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2000
Volume 25, Issue 27
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

Abstract

The global rise of drug-resistant malaria parasites is becoming an increasing threat to public health, emphasizing the urgent need for the development of new therapeutic strategies. Artimisinin-based therapies, once the backbone of malaria treatment, are now at risk due to the resistance developed in parasites. The lack of a universally accessible malaria vaccine exacerbates this crisis, underscoring the need to explore new antimalarial drugs. A more comprehensive understanding of the parasites’s life cycle has revealed several promising targets, including enzymes, transport proteins, and essential metabolic pathways that the parasite relies on for its survival and proliferation. This review provides an in-depth analysis of the vulnerabilities displayed by Plasmodium and recent advances that highlight potential drug targets and candidate molecules.

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References

  1. WhitfieldJ. Portrait of a serial killer.Nature2002news021001610.1038/news021001‑6
    [Google Scholar]
  2. world malaria reportAvailable from: https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2023 2023
  3. ShibeshiM.A. KifleZ.D. AtnafieS.A. Antimalarial drug resistance and novel targets for antimalarial drug discovery.Infect. Drug Resist.2020134047406010.2147/IDR.S279433 33204122
    [Google Scholar]
  4. WardK.E. FidockD.A. BridgfordJ.L. Plasmodium falciparum resistance to artemisinin-based combination therapies.Curr. Opin. Microbiol.20226910219310.1016/j.mib.2022.102193 36007459
    [Google Scholar]
  5. CoxF.E.G. History of the discovery of the malaria parasites and their vectors.Parasit. Vectors201031510.1186/1756‑3305‑3‑5 20205846
    [Google Scholar]
  6. ParryJ. WHO combats counterfeit malaria drugs in Asia.BMJ20053301044.510.1136/bmj.330.7499.1044‑d
    [Google Scholar]
  7. VenugopalK. HentzschelF. ValkiūnasG. MartiM. Plasmodium asexual growth and sexual development in the haematopoietic niche of the host.Nat. Rev. Microbiol.202018317718910.1038/s41579‑019‑0306‑2 31919479
    [Google Scholar]
  8. OuologuemD.T. DaraA. KoneA. OuattaraA. DjimdeA.A. Plasmodium falciparum development from gametocyte to oocyst: Insight from functional studies.Microorganisms2023118196610.3390/microorganisms11081966 37630530
    [Google Scholar]
  9. SatoS. Plasmodium—a brief introduction to the parasites causing human malaria and their basic biology.J. Physiol. Anthropol.2021401110.1186/s40101‑020‑00251‑9 33413683
    [Google Scholar]
  10. RaiS. ShuklaS. ScottiL. ManiA. Drug repurposing against novel therapeutic targets in Plasmodium falciparum for Malaria: The computational perspective.Curr. Med. Chem.202431386272628710.2174/0929867331666230807151708 37550911
    [Google Scholar]
  11. CounihanN.A. ModakJ.K. de Koning-WardT.F. How Malaria parasites acquire nutrients from their host.Front. Cell Dev. Biol.2021964918410.3389/fcell.2021.649184 33842474
    [Google Scholar]
  12. BanerjeeR. GoldbergD.E. The plasmodium food vacuole. Antimalar. Chemother. Mech. Action Resist. New Dir. Drug Discov. RosenthalP.J. Totowa, NJHumana Press20014363
    [Google Scholar]
  13. BonillaJ.A. BonillaT.D. YowellC.A. FujiokaH. DameJ.B. Critical roles for the digestive vacuole plasmepsins of Plasmodium falciparum in vacuolar function.Mol. Microbiol.2007651647510.1111/j.1365‑2958.2007.05768.x 17581121
    [Google Scholar]
  14. MouraI.C. WunderlichG. UhrigM.L. CoutoA.S. PeresV.J. KatzinA.M. KimuraE.A. Limonene arrests parasite development and inhibits isoprenylation of proteins in Plasmodium falciparum.Antimicrob. Agents Chemother.20014592553255810.1128/AAC.45.9.2553‑2558.2001 11502528
    [Google Scholar]
  15. LiuJ. GluzmanI.Y. DrewM.E. GoldbergD.E. The role of Plasmodium falciparum food vacuole plasmepsins.J. Biol. Chem.200528021432143710.1074/jbc.M409740200 15513918
    [Google Scholar]
  16. KlembaM. GluzmanI. GoldbergD.E. A Plasmodium falciparum dipeptidyl aminopeptidase I participates in vacuolar hemoglobin degradation.J. Biol. Chem.200427941430004300710.1074/jbc.M408123200 15304495
    [Google Scholar]
  17. DrewM.E. BanerjeeR. UffmanE.W. GilbertsonS. RosenthalP.J. GoldbergD.E. Plasmodium food vacuole plasmepsins are activated by falcipains.J. Biol. Chem.200828319128701287610.1074/jbc.M708949200 18308731
    [Google Scholar]
  18. PatrickG.L. Plasmepsins as targets for antimalarial agents. Antimalar. Agents.Elsevier202021727010.1016/B978‑0‑08‑101210‑9.00007‑X
    [Google Scholar]
  19. SunilS. ChauhanV.S. MalhotraP. Distinct and stage specific nuclear factors regulate the expression of falcipains, Plasmodium falciparum cysteine proteases.BMC Mol. Biol.2008914710.1186/1471‑2199‑9‑47 18477411
    [Google Scholar]
  20. GoldbergD.E. SlaterA.F. BeavisR. ChaitB. CeramiA. HendersonG.B. Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: A catabolic pathway initiated by a specific aspartic protease.J. Exp. Med.1991173496196910.1084/jem.173.4.961 2007860
    [Google Scholar]
  21. PadmanabanG. NagarajV.A. RangarajanP.N. Drugs and drug targets against malaria.Curr. Sci.20079215451555
    [Google Scholar]
  22. KrugliakM. ZhangJ. GinsburgH. Intraerythrocytic Plasmodium falciparum utilizes only a fraction of the amino acids derived from the digestion of host cell cytosol for the biosynthesis of its proteins.Mol. Biochem. Parasitol.2002119224925610.1016/S0166‑6851(01)00427‑3 11814576
    [Google Scholar]
  23. RohrbachP. RohrbachP. DaltonJ.P. The malaria digestive vacuole.Front. Biosci.2012S441424144810.2741/s344 22652884
    [Google Scholar]
  24. AndrewsK.T. FairlieD.P. MadalaP.K. RayJ. WyattD.M. HiltonP.M. MelvilleL.A. BeattieL. GardinerD.L. ReidR.C. StoermerM.J. Skinner-AdamsT. BerryC. McCarthyJ.S. Potencies of human immunodeficiency virus protease inhibitors in vitro against Plasmodium falciparum and in vivo against murine malaria.Antimicrob. Agents Chemother.200650263964810.1128/AAC.50.2.639‑648.2006 16436721
    [Google Scholar]
  25. BhagavathulaA.S. ElnourA.A. ShehabA. Alternatives to currently used antimalarial drugs: In search of a magic bullet.Infect. Dis. Poverty20165110310.1186/s40249‑016‑0196‑8 27809883
    [Google Scholar]
  26. RajR. KumarV. Anti‐malarial drug discovery: New enzyme inhibitors. Nat. Prod. Target. Clin. Relev. Enzym1st ed AndradeP.B. ValentãoP. PereiraD.M. Wiley201727729610.1002/9783527805921.ch11
    [Google Scholar]
  27. AmeloW. MakonnenE. Efforts made to eliminate drug-resistant malaria and its challenges.BioMed Res. Int.20212021553954410.1155/2021/5539544
    [Google Scholar]
  28. MavondoG.A. MkhwananziB.N. MabandlaM.V. Pre-infection administration of asiatic acid retards parasitaemia induction in Plasmodium berghei murine malaria infected Sprague-Dawley rats.Malar. J.201615122610.1186/s12936‑016‑1278‑6 27098750
    [Google Scholar]
  29. CoppéeR. SabbaghA. ClainJ. Structural and evolutionary analyses of the Plasmodium falciparum chloroquine resistance transporter.Sci. Rep.2020101484210.1038/s41598‑020‑61181‑1 32179795
    [Google Scholar]
  30. BergerF. GomezG.M. SanchezC.P. PoschB. PlanellesG. SohrabyF. Nunes-AlvesA. LanzerM. pH-dependence of the Plasmodium falciparum chloroquine resistance transporter is linked to the transport cycle.Nat. Commun.2023141423410.1038/s41467‑023‑39969‑2 37454114
    [Google Scholar]
  31. EhlgenF. PhamJ.S. de Koning-WardT. CowmanA.F. RalphS.A. Investigation of the Plasmodium falciparum food vacuole through inducible expression of the chloroquine resistance transporter (PfCRT).PLoS One201276e3878110.1371/journal.pone.0038781 22719945
    [Google Scholar]
  32. SanchezC.P. SteinW.D. LanzerM. Is PfCRT a channel or a carrier? Two competing models explaining chloroquine resistance in Plasmodium falciparum.Trends Parasitol.200723733233910.1016/j.pt.2007.04.013 17493873
    [Google Scholar]
  33. Amambua-NgwaA. Button-SimonsK.A. LiX. KumarS. BrennemanK.V. FerrariM. CheckleyL.A. HaileM.T. ShoueD.A. McDew-WhiteM. TindallS.M. ReyesA. DelgadoE. DalhoffH. LarbalestierJ.K. AmatoR. PearsonR.D. TaylorA.B. NostenF.H. D’AlessandroU. KwiatkowskiD. CheesemanI.H. KappeS.H.I. AveryS.V. ConwayD.J. VaughanA.M. FerdigM.T. AndersonT.J.C. An amino acid transporter AAT1 plays a pivotal role in chloroquine resistance evolution in malaria parasites.bioRxiv202210.1101/2022.05.26.493611
    [Google Scholar]
  34. CoronadoL.M. NadovichC.T. SpadaforaC. Malarial hemozoin: From target to tool.Biochim. Biophys. Acta, Gen. Subj.2014184062032204110.1016/j.bbagen.2014.02.009 24556123
    [Google Scholar]
  35. HempelmannE. Hemozoin biocrystallization in Plasmodium falciparum and the antimalarial activity of crystallization inhibitors.Parasitol. Res.2007100467167610.1007/s00436‑006‑0313‑x 17111179
    [Google Scholar]
  36. GuptaP. PandeyR. ThakurV. ParveenS. KaurI. PandaA. BishiR. MehrotraS. AkhtarA. GuptaD. MohmmedA. MalhotraP. Heme detoxification protein (PF HDP) is essential for the hemoglobin uptake and metabolism in Plasmodium falciparum.FASEB Bioadv.202241066267410.1096/fba.2022‑00021 36238365
    [Google Scholar]
  37. NakataniK. IshikawaH. AonoS. MizutaniY. Heme-binding properties of heme detoxification protein from Plasmodium falciparum.Biochem. Biophys. Res. Commun.2013439447748010.1016/j.bbrc.2013.08.100 24025682
    [Google Scholar]
  38. KapishnikovS. HempelmannE. ElbaumM. Als-NielsenJ. LeiserowitzL. Malaria pigment crystals: The achilles′ heel of the malaria parasite.ChemMedChem202116101515153210.1002/cmdc.202000895 33523575
    [Google Scholar]
  39. OlafsonK.N. KetchumM.A. RimerJ.D. VekilovP.G. Mechanisms of hematin crystallization and inhibition by the antimalarial drug chloroquine.Proc. Natl. Acad. Sci. USA2015112164946495110.1073/pnas.1501023112 25831526
    [Google Scholar]
  40. OlivierM. Van Den HamK. ShioM.T. KassaF.A. FougerayS. Malarial pigment hemozoin and the innate inflammatory response.Front. Immunol.201452510.3389/fimmu.2014.00025 24550911
    [Google Scholar]
  41. GuptaM. KumarS. KumarR. KumarA. VermaR. DarokarM.P. RoutP. PalA. Inhibition of heme detoxification pathway in malaria parasite by 3-hydroxy-11-keto-β-boswellic acid isolated from Boswellia serrata.Biomed. Pharmacother.202114411230210.1016/j.biopha.2021.112302 34678731
    [Google Scholar]
  42. MaliS.N. PandeyA. Hemozoin (beta-hematin) formation inhibitors: Promising target for the development of new antimalarials: Current update and future prospect.Comb. Chem. High Throughput Screen.202225111859187410.2174/1386207325666210924104036 34565319
    [Google Scholar]
  43. SullivanD.J.Jr GluzmanI.Y. GoldbergD.E. Plasmodium hemozoin formation mediated by histidine-rich proteins.Science1996271524621922210.1126/science.271.5246.219 8539625
    [Google Scholar]
  44. EdgarR.C.S. CounihanN.A. McGowanS. de Koning-WardT.F. Methods used to investigate the Plasmodium falciparum digestive vacuole.Front. Cell. Infect. Microbiol.20221182982310.3389/fcimb.2021.829823 35096663
    [Google Scholar]
  45. TilleyL. StraimerJ. GnädigN.F. RalphS.A. FidockD.A. Artemisinin action and resistance in Plasmodium falciparum.Trends Parasitol.201632968269610.1016/j.pt.2016.05.010 27289273
    [Google Scholar]
  46. KannanR. SahalD. ChauhanV.S. Heme-artemisinin adducts are crucial mediators of the ability of artemisinin to inhibit heme polymerization.Chem. Biol.20029332133210.1016/S1074‑5521(02)00117‑5 11927257
    [Google Scholar]
  47. GiannangeloC. SiddiquiG. De PaoliA. AndersonB.M. Edgington-MitchellL.E. CharmanS.A. CreekD.J. System-wide biochemical analysis reveals ozonide antimalarials initially act by disrupting Plasmodium falciparum haemoglobin digestion.PLoS Pathog.2020166e100848510.1371/journal.ppat.1008485 32589689
    [Google Scholar]
  48. MengueJ.B. HeldJ. KreidenweissA. AQ-13 - An investigational antimalarial drug.Expert Opin. Investig. Drugs201928321722210.1080/13543784.2019.1560419 30577704
    [Google Scholar]
  49. UmumararunguT. NkurangaJ.B. HabaruremaG. NyandwiJ.B. MukazayireM.J. MukizaJ. MugangaR. HahirwaI. MpendaM. KatembeziA.N. OlawodeE.O. KayitareE. KayumbaP.C. Recent developments in antimalarial drug discovery.Bioorg. Med. Chem.202388-8911733910.1016/j.bmc.2023.117339 37236020
    [Google Scholar]
  50. BalestraA.C. ZeeshanM. ReaE. PasquarelloC. BrusiniL. MourierT. SubudhiA.K. KlagesN. ArboitP. PandeyR. BradyD. VaughanS. HolderA.A. PainA. FergusonD.J.P. HainardA. TewariR. BrochetM. A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of a malaria parasite during gametogony and transmission.eLife20209e5647410.7554/eLife.56474 32568069
    [Google Scholar]
  51. HalbertJ. AyongL. EquinetL. Le RochK. HardyM. GoldringD. ReiningerL. WatersN. ChakrabartiD. DoerigC. A Plasmodium falciparum transcriptional cyclin-dependent kinase-related kinase with a crucial role in parasite proliferation associates with histone deacetylase activity.Eukaryot. Cell20109695295910.1128/EC.00005‑10 20305001
    [Google Scholar]
  52. SolyakovL. HalbertJ. AlamM.M. SemblatJ.P. Dorin-SemblatD. ReiningerL. BottrillA.R. MistryS. AbdiA. FennellC. HollandZ. DemartaC. BouzaY. SicardA. NivezM.P. EschenlauerS. LamaT. ThomasD.C. SharmaP. AgarwalS. KernS. PradelG. GraciottiM. TobinA.B. DoerigC. Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum.Nat. Commun.20112156510.1038/ncomms1558 22127061
    [Google Scholar]
  53. KumarS. GargaroO.R. KappeS.H.I. Plasmodium falciparum CRK5 is critical for male gametogenesis and infection of the mosquito.MBio2022135e022272210.1128/mbio.02227‑22 36154191
    [Google Scholar]
  54. Le RochK. SestierC. DorinD. WatersN. KappesB. ChakrabartiD. MeijerL. DoerigC. Activation of a Plasmodium falciparum cdc2-related kinase by heterologous p25 and cyclin H. Functional characterization of a P. falciparum cyclin homologue.J. Biol. Chem.2000275128952895810.1074/jbc.275.12.8952 10722743
    [Google Scholar]
  55. JirageD. ChenY. CaridhaD. O’NeilM.T. EyaseF. WitolaW.H. MamounC.B. WatersN.C. The malarial CDK Pfmrk and its effector PfMAT1 phosphorylate DNA replication proteins and co-localize in the nucleus.Mol. Biochem. Parasitol.2010172191810.1016/j.molbiopara.2010.03.009 20332005
    [Google Scholar]
  56. WatersN. WoodardC.L. PriggeS.T. Cyclin H activation and drug susceptibility of the Pfmrk cyclin dependent protein kinase from Plasmodium falciparum.Mol. Biochem. Parasitol.20001071455510.1016/S0166‑6851(99)00229‑7 10717301
    [Google Scholar]
  57. RobbinsJ.A. AbsalonS. StrevaV.A. DvorinJ.D. The Malaria parasite cyclin H homolog PfCyc1 is required for efficient cytokinesis in blood-stage Plasmodium falciparum.MBio201783e00605e0061710.1128/mBio.00605‑17 28611247
    [Google Scholar]
  58. GanterM. GoldbergJ.M. DvorinJ.D. PauloJ.A. KingJ.G. TripathiA.K. PaulA.S. YangJ. CoppensI. JiangR.H.Y. ElsworthB. BakerD.A. DinglasanR.R. GygiS.P. DuraisinghM.T. Plasmodium falciparum CRK4 directs continuous rounds of DNA replication during schizogony.Nat. Microbiol.2017251701710.1038/nmicrobiol.2017.17 28211852
    [Google Scholar]
  59. EubanksA.L. PerkinsM.M. SylvesterK. GanleyJ.G. PosfaiD. SanschargrinP.C. HongJ. SlizP. DerbyshireE.R. In silico screening and evaluation of Plasmodium falciparum protein kinase 5 (PK5) inhibitors.ChemMedChem201813232479248310.1002/cmdc.201800625 30328274
    [Google Scholar]
  60. Bracchi-RicardV. BarikS. DelvecchioC. DoerigC. ChakrabartiR. ChakrabartiD. PfPK6, a novel cyclin-dependent kinase/mitogen-activated protein kinase-related protein kinase from Plasmodium falciparum.Biochem. J.2000347125526310.1042/bj3470255 10727426
    [Google Scholar]
  61. MatthewsH. DuffyC.W. MerrickC.J. Checks and balances? DNA replication and the cell cycle in Plasmodium.Parasit. Vectors201811121610.1186/s13071‑018‑2800‑1 29587837
    [Google Scholar]
  62. GrayK.A. GrestyK.J. ChenN. ZhangV. GutteridgeC.E. PeateyC.L. ChavchichM. WatersN.C. ChengQ. Correlation between cyclin dependent kinases and artemisinin-induced dormancy in Plasmodium falciparumin vitro.PLoS One2016116e015790610.1371/journal.pone.0157906 27326764
    [Google Scholar]
  63. ChakrabortyA. Understanding the biology of the Plasmodium falciparum apicoplast; An excellent target for antimalarial drug development.Life Sci.201615810411010.1016/j.lfs.2016.06.030 27381078
    [Google Scholar]
  64. WilsonR.J.M.I. Parasite plastids: Approaching the endgame.Biol. Rev. Camb. Philos. Soc.200580112915310.1017/S1464793104006591 15727041
    [Google Scholar]
  65. HeathR.J. RockC.O. Fatty acid biosynthesis as a target for novel antibacterials.Curr. Opin. Investig. Drugs200452146153 15043388
    [Google Scholar]
  66. PriggeS.T. HeX. GerenaL. WatersN.C. ReynoldsK.A. The initiating steps of a type II fatty acid synthase in Plasmodium falciparum are catalyzed by pfACP, pfMCAT, and pfKASIII.Biochemistry20034241160116910.1021/bi026847k 12549938
    [Google Scholar]
  67. ShearsM.J. BottéC.Y. McFaddenG.I. Fatty acid metabolism in the Plasmodium apicoplast: Drugs, doubts and knockouts.Mol. Biochem. Parasitol.20151991-2345010.1016/j.molbiopara.2015.03.004 25841762
    [Google Scholar]
  68. van SchaijkB.C.L. KumarT.R.S. VosM.W. RichmanA. van GemertG.J. LiT. EappenA.G. WilliamsonK.C. MorahanB.J. FishbaugherM. KennedyM. CamargoN. KhanS.M. JanseC.J. SimK.L. HoffmanS.L. KappeS.H.I. SauerweinR.W. FidockD.A. VaughanA.M. TypeI.I. Type II fatty acid biosynthesis is essential for Plasmodium falciparum sporozoite development in the midgut of Anopheles mosquitoes.Eukaryot. Cell201413555055910.1128/EC.00264‑13 24297444
    [Google Scholar]
  69. VaughanA.M. O’NeillM.T. TarunA.S. CamargoN. PhuongT.M. AlyA.S.I. CowmanA.F. KappeS.H.I. Type II fatty acid synthesis is essential only for malaria parasite late liver stage development.Cell. Microbiol.200911350652010.1111/j.1462‑5822.2008.01270.x 19068099
    [Google Scholar]
  70. McLeodR. MuenchS.P. RaffertyJ.B. KyleD.E. MuiE.J. KirisitsM.J. MackD.G. RobertsC.W. SamuelB.U. LyonsR.E. DorrisM. MilhousW.K. RiceD.W. Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of Apicomplexan Fab I.Int. J. Parasitol.200131210911310.1016/S0020‑7519(01)00111‑4 11239932
    [Google Scholar]
  71. RamyaT.N.C. MishraS. KarmodiyaK. SuroliaN. SuroliaA. Inhibitors of nonhousekeeping functions of the apicoplast defy delayed death in Plasmodium falciparum.Antimicrob. Agents Chemother.200751130731610.1128/AAC.00808‑06 17060533
    [Google Scholar]
  72. BommineniG.R. KapilashramiK. CummingsJ.E. LuY. KnudsonS.E. GuC. WalkerS.G. SlaydenR.A. TongeP.J. Thiolactomycin-based inhibitors of bacterial β-ketoacyl-ACP synthases with in vivo activity.J. Med. Chem.201659115377539010.1021/acs.jmedchem.6b00236 27187871
    [Google Scholar]
  73. LeeP.J. BhonsleJ.B. GaonaH.W. HuddlerD.P. HeadyT.N. Kreishman-DeitrickM. BhattacharjeeA. McCalmontW.F. GerenaL. Lopez-SanchezM. RoncalN.E. HudsonT.H. JohnsonJ.D. PriggeS.T. WatersN.C. Targeting the fatty acid biosynthesis enzyme, beta-ketoacyl-acyl carrier protein synthase III (PfKASIII), in the identification of novel antimalarial agents.J. Med. Chem.200952495296310.1021/jm8008103 19191586
    [Google Scholar]
  74. BiddauM. SheinerL. Targeting the apicoplast in malaria.Biochem. Soc. Trans.201947497398310.1042/BST20170563 31383817
    [Google Scholar]
  75. SinghD. ChaubeyS. HabibS. Replication of the Plasmodium falciparum apicoplast DNA initiates within the inverted repeat region.Mol. Biochem. Parasitol.2003126191410.1016/S0166‑6851(02)00251‑7 12554079
    [Google Scholar]
  76. LowL.M. StanisicD.I. GoodM.F. Exploiting the apicoplast: Apicoplast-targeting drugs and malaria vaccine development.Microbes Infect.2018209-1047748310.1016/j.micinf.2017.12.005 29287981
    [Google Scholar]
  77. PradinesB. RogierC. FusaiT. MosnierJ. DariesW. BarretE. ParzyD. In vitro activities of antibiotics against Plasmodium falciparum are inhibited by iron.Antimicrob. Agents Chemother.20014561746175010.1128/AAC.45.6.1746‑1750.2001 11353621
    [Google Scholar]
  78. UddinT. McFaddenG.I. GoodmanC.D. Validation of putative apicoplast-targeting drugs using a chemical supplementation assay in cultured human malaria parasites.Antimicrob. Agents Chemother.2018621e011611710.1128/AAC.01161‑17 29109165
    [Google Scholar]
  79. FontinhaD. MoulesI. PrudêncioM. Repurposing drugs to fight hepatic malaria parasites.Molecules20202515340910.3390/molecules25153409 32731386
    [Google Scholar]
  80. SlaterA.F.G. CeramiA. Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites.Nature1992355635616716910.1038/355167a0 1729651
    [Google Scholar]
  81. DahlE.L. RosenthalP.J. Apicoplast translation, transcription and genome replication: Targets for antimalarial antibiotics.Trends Parasitol.200824627928410.1016/j.pt.2008.03.007 18450512
    [Google Scholar]
  82. GisselbergJ.E. Dellibovi-RaghebT.A. MatthewsK.A. BoschG. PriggeS.T. The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites.PLoS Pathog.201399e100365510.1371/journal.ppat.1003655 24086138
    [Google Scholar]
  83. CharanM. ChoudharyH.H. SinghN. SadikM. SiddiqiM.I. MishraS. HabibS. [Fe-S] cluster assembly in the apicoplast and its indispensability in mosquito stages of the malaria parasite.FEBS J.2017284162629264810.1111/febs.14159 28695709
    [Google Scholar]
  84. RöhrichR.C. EnglertN. TroschkeK. ReichenbergA. HintzM. SeeberF. BalconiE. AlivertiA. ZanettiG. KöhlerU. PfeifferM. BeckE. JomaaH. WiesnerJ. Reconstitution of an apicoplast‐localised electron transfer pathway involved in the isoprenoid biosynthesis of Plasmodium falciparum.FEBS Lett.2005579286433643810.1016/j.febslet.2005.10.037 16289098
    [Google Scholar]
  85. AltincicekB. DuinE.C. ReichenbergA. HedderichR. KollasA.K. HintzM. WagnerS. WiesnerJ. BeckE. JomaaH. LytB protein catalyzes the terminal step of the 2‐ C ‐methyl‐ D ‐erythritol‐4‐phosphate pathway of isoprenoid biosynthesis.FEBS Lett.2002532343744010.1016/S0014‑5793(02)03726‑2 12482608
    [Google Scholar]
  86. KollasA.K. DuinE.C. EberlM. AltincicekB. HintzM. ReichenbergA. HenschkerD. HenneA. SteinbrecherI. OstrovskyD.N. HedderichR. BeckE. JomaaH. WiesnerJ. Functional characterization of GcpE, an essential enzyme of the non‐mevalonate pathway of isoprenoid biosynthesis.FEBS Lett.2002532343243610.1016/S0014‑5793(02)03725‑0 12482607
    [Google Scholar]
  87. ThipubonP. UthaipibullC. KamchonwongpaisanS. TipsuwanW. SrichairatanakoolS. Inhibitory effect of novel iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) and green tea extract on growth of Plasmodium falciparum.Malar. J.201514138210.1186/s12936‑015‑0910‑1 26424148
    [Google Scholar]
  88. ThumaP.E. OlivieriN.F. MabezaG.F. BiembaG. ParryD. ZuluS. FassosF.F. McClellandR.A. KorenG. BrittenhamG.M. GordeukV.R. Assessment of the effect of the oral iron chelator deferiprone on asymptomatic Plasmodium falciparum parasitemia in humans.Am. J. Trop. Med. Hyg.199858335836410.4269/ajtmh.1998.58.358 9546419
    [Google Scholar]
  89. IheanachoE.N. SamuniA. Avramovici-GrisaruS. SarelS. SpiraD.T. Inhibition of Plasmodium falciparum growth by a synthetic iron chelator.Trans. R. Soc. Trop. Med. Hyg.199084221321610.1016/0035‑9203(90)90259‑H 2202102
    [Google Scholar]
  90. HeinyS.R. PautzS. ReckerM. PrzyborskiJ.M. Protein Traffic to the Plasmodium falciparum apicoplast: evidence for a sorting branch point at the Golgi.Traffic201415121290130410.1111/tra.12226 25264207
    [Google Scholar]
  91. ParsonsM. KarnatakiA. FeaginJ.E. DeRocherA. Protein trafficking to the apicoplast: Deciphering the apicomplexan solution to secondary endosymbiosis.Eukaryot. Cell2007671081108810.1128/EC.00102‑07 17513565
    [Google Scholar]
  92. CraigE.A. GambillB.D. NelsonR.J. Heat shock proteins: Molecular chaperones of protein biogenesis.Microbiol. Rev.199357240241410.1128/mr.57.2.402‑414.1993 8336673
    [Google Scholar]
  93. GitauG.W. MandalP. BlatchG.L. PrzyborskiJ. ShonhaiA. Characterisation of the Plasmodium falciparum Hsp70-Hsp90 organising protein (PfHop).Cell Stress Chaperones201217219120210.1007/s12192‑011‑0299‑x 22005844
    [Google Scholar]
  94. FlorentinA. CobbD.W. FishburnJ.D. CiprianoM.J. KimP.S. FierroM.A. StriepenB. MuralidharanV. PfClpC is an essential clp chaperone required for plastid integrity and Clp protease stability in Plasmodium falciparum.Cell Rep.20172171746175610.1016/j.celrep.2017.10.081 29141210
    [Google Scholar]
  95. El BakkouriM. PowA. MulichakA. CheungK.L.Y. ArtzJ.D. AmaniM. FellS. de Koning-WardT.F. GoodmanC.D. McFaddenG.I. OrtegaJ. HuiR. HouryW.A. The Clp chaperones and proteases of the human malaria parasite Plasmodium falciparum.J. Mol. Biol.2010404345647710.1016/j.jmb.2010.09.051 20887733
    [Google Scholar]
  96. ZiningaT. PooeO.J. MakhadoP.B. RamatsuiL. PrinslooE. AchilonuI. DirrH. ShonhaiA. Polymyxin B inhibits the chaperone activity of Plasmodium falciparum Hsp70.Cell Stress Chaperones201722570771510.1007/s12192‑017‑0797‑6 28455613
    [Google Scholar]
  97. ZiningaT. ShonhaiA. Small molecule inhibitors targeting the heat shock protein system of human obligate protozoan parasites.Int. J. Mol. Sci.20192023593010.3390/ijms20235930 31775392
    [Google Scholar]
  98. EklandE.H. SchneiderJ. FidockD.A. Identifying apicoplast‐targeting antimalarials using high‐throughput compatible approaches.FASEB J.201125103583359310.1096/fj.11‑187401 21746861
    [Google Scholar]
  99. BiddauM. KumarT.R.S. HenrichP. LaineL.M. BlackburnG.J. ChokkathukalamA. LiT.B. SimK.L. HoffmanS.L. BarrettM.P. CoombsG.H. McFaddenG.I. FidockD.A. MüllerS. SheinerL. Lipoic acid biosynthesis is essential for Plasmodium falciparum transmission and influences redox response and carbon metabolism of parasite asexual blood stages.Cell Biol.202010.1101/2020.05.17.099630
    [Google Scholar]
  100. FalkardB. KumarT.R.S. HechtL.S. MatthewsK.A. HenrichP.P. GulatiS. LewisR.E. ManaryM.J. WinzelerE.A. SinnisP. PriggeS.T. HeusslerV. DeschermeierC. FidockD. A key role for lipoic acid synthesis during Plasmodium liver stage development.Cell. Microbiol.20131591585160410.1111/cmi.12137 23490300
    [Google Scholar]
  101. Rei YanS.L. WakasuquiF. DuX. GrovesM.R. WrengerC. Lipoic acid metabolism as a potential chemotherapeutic target against Plasmodium falciparum and Staphylococcus aureus.Front Chem.2021974217510.3389/fchem.2021.742175 34805091
    [Google Scholar]
  102. BiddauM. Santha KumarT.R. HenrichP. LaineL.M. BlackburnG.J. ChokkathukalamA. LiT. Lee SimK. KingL. HoffmanS.L. BarrettM.P. CoombsG.H. McFaddenG.I. FidockD.A. MüllerS. SheinerL. Plasmodium falciparum LipB mutants display altered redox and carbon metabolism in asexual stages and cannot complete sporogony in Anopheles mosquitoes.Int. J. Parasitol.202151644145310.1016/j.ijpara.2020.10.011 33713652
    [Google Scholar]
  103. StormJ. MüllerS. Lipoic acid metabolism of Plasmodium--a suitable drug target.Curr. Pharm. Des.201218243480348910.2174/138161212801327266 22607141
    [Google Scholar]
  104. FothB.J. StimmlerL.M. HandmanE. CrabbB.S. HodderA.N. McFaddenG.I. The malaria parasite Plasmodium falciparum has only one pyruvate dehydrogenase complex, which is located in the apicoplast.Mol. Microbiol.2005551395310.1111/j.1365‑2958.2004.04407.x 15612915
    [Google Scholar]
  105. Thomsen-ZiegerN. SchachtnerJ. SeeberF. Apicomplexan parasites contain a single lipoic acid synthase located in the plastid.FEBS Lett.20035471-3808610.1016/S0014‑5793(03)00673‑2 12860390
    [Google Scholar]
  106. WangM. WangQ. GaoX. SuZ. Conditional knock-out of lipoic acid protein ligase 1 reveals redundancy pathway for lipoic acid metabolism in Plasmodium berghei malaria parasite.Parasit. Vectors201710131510.1186/s13071‑017‑2253‑y 28655332
    [Google Scholar]
  107. AllaryM. LuJ.Z. ZhuL. PriggeS.T. Scavenging of the cofactor lipoate is essential for the survival of the malaria parasite Plasmodium falciparum.Mol. Microbiol.20076351331134410.1111/j.1365‑2958.2007.05592.x 17244193
    [Google Scholar]
  108. GüntherS. MatuschewskiK. MüllerS. Knockout studies reveal an important role of Plasmodium lipoic acid protein ligase A1 for asexual blood stage parasite survival.PLoS One200945e551010.1371/journal.pone.0005510 19434237
    [Google Scholar]
  109. BansalA. Molina-CruzA. BrzostowskiJ. LiuP. LuoY. GunalanK. LiY. RibeiroJ.M.C. MillerL.H. Pf CDPK1 is critical for malaria parasite gametogenesis and mosquito infection.Proc. Natl. Acad. Sci. USA2018115477477910.1073/pnas.1715443115 29311293
    [Google Scholar]
  110. KumarS. HaileM.T. HoopmannM.R. TranL.T. MichaelsS.A. MorroneS.R. OjoK.K. ReynoldsL.M. KusebauchU. VaughanA.M. MoritzR.L. KappeS.H.I. SwearingenK.E. Plasmodium falciparum calcium-dependent protein kinase 4 is critical for male gametogenesis and transmission to the mosquito vector.MBio2021126e025752110.1128/mBio.02575‑21 34724830
    [Google Scholar]
  111. AbsalonS. BlomqvistK. RudlaffR.M. DeLanoT.J. PollastriM.P. DvorinJ.D. Calcium-dependent protein kinase 5 is required for release of egress-specific organelles in Plasmodium falciparum.MBio201891e001301810.1128/mBio.00130‑18 29487234
    [Google Scholar]
  112. BlomqvistK. HelmelM. WangC. AbsalonS. LabunskaT. RudlaffR.M. AdapaS. JiangR. SteenH. DvorinJ.D. Influence of Plasmodium falciparum calcium-dependent protein kinase 5 (PfCDPK5) on the late schizont stage phosphoproteome.MSphere202051e009211910.1128/mSphere.00921‑19 31915223
    [Google Scholar]
  113. KumarP. TripathiA. RanjanR. HalbertJ. GilbergerT. DoerigC. SharmaP. Regulation of Plasmodium falciparum development by calcium-dependent protein kinase 7 (PfCDPK7).J. Biol. Chem.201428929203862039510.1074/jbc.M114.561670 24895132
    [Google Scholar]
  114. KumarS. KumarM. EkkaR. DvorinJ.D. PaulA.S. MadugunduA.K. GilbergerT. GowdaH. DuraisinghM.T. Keshava PrasadT.S. SharmaP. PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium falciparum.Nat. Commun.2017816310.1038/s41467‑017‑00053‑1 28680058
    [Google Scholar]
  115. MauryaR. TripathiA. KumarM. AntilN. Yamaryo-BottéY. KumarP. BansalP. DoerigC. BottéC.Y. PrasadT.S.K. SharmaP. PI4‐kinase and PfCDPK7 signaling regulate phospholipid biosynthesis in Plasmodium falciparum.EMBO Rep.2022232e5402210.15252/embr.202154022 34866326
    [Google Scholar]
  116. Siden-KiamosI. EckerA. NybäckS. LouisC. SindenR.E. BillkerO. Plasmodium berghei calcium‐dependent protein kinase 3 is required for ookinete gliding motility and mosquito midgut invasion.Mol. Microbiol.20066061355136310.1111/j.1365‑2958.2006.05189.x 16796674
    [Google Scholar]
  117. RaiP. SharmaD. SoniR. KhatoonN. SharmaB. BhattT.K. Plasmodium falciparum apicoplast and its transcriptional regulation through calcium signaling.J. Microbiol.201755423123610.1007/s12275‑017‑6525‑1 28251546
    [Google Scholar]
  118. CasseraM.B. GozzoF.C. D’AlexandriF.L. MerinoE.F. del PortilloH.A. PeresV.J. AlmeidaI.C. EberlinM.N. WunderlichG. WiesnerJ. JomaaH. KimuraE.A. KatzinA.M. The methylerythritol phosphate pathway is functionally active in all intraerythrocytic stages of Plasmodium falciparum.J. Biol. Chem.200427950517495175910.1074/jbc.M408360200 15452112
    [Google Scholar]
  119. OkadaM. RajaramK. SwiftR.P. MixonA. MaschekJ.A. PriggeS.T. SigalaP.A. Critical role for isoprenoids in apicoplast biogenesis by malaria parasites.eLife202211e7320810.7554/eLife.73208 35257658
    [Google Scholar]
  120. GuggisbergA.M. AmthorR.E. OdomA.R. Isoprenoid biosynthesis in Plasmodium falciparum.Eukaryot. Cell201413111348135910.1128/EC.00160‑14 25217461
    [Google Scholar]
  121. SagguG.S. PalaZ.R. GargS. SaxenaV. New insight into isoprenoids biosynthesis process and future prospects for drug designing in plasmodium.Front. Microbiol.20167142110.3389/fmicb.2016.01421 27679614
    [Google Scholar]
  122. HoweR. KellyM. JimahJ. HodgeD. OdomA.R. Isoprenoid biosynthesis inhibition disrupts Rab5 localization and food vacuolar integrity in Plasmodium falciparum.Eukaryot. Cell201312221522310.1128/EC.00073‑12 23223036
    [Google Scholar]
  123. E.A. Kimura, G. Wunderlich, F.M. Jordão, R. Tonhosolo, H.B. Gabriel, R.A.C. Sussmann, A.Y. Saito, A.M. Katzin. Use of Radioactive Precursors for Biochemical Characterization the Biosynthesis of Isoprenoids in Intraerythrocytic Stages of Plasmodium falciparum. In: Radioisotopes - Applications in Bio-Medical Science.InTech201110.5772/20582
    [Google Scholar]
  124. CasseraM.B. MerinoE.F. PeresV.J. KimuraE.A. WunderlichG. KatzinA.M. Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum.Mem. Inst. Oswaldo Cruz2007102337738410.1590/S0074‑02762007000300019 17568945
    [Google Scholar]
  125. SagguG.S. Apicoplast journey and its essentiality as a compartment for malaria parasite survival.Front. Cell. Infect. Microbiol.20221288182510.3389/fcimb.2022.881825 35463632
    [Google Scholar]
  126. ChakrabartiD. Da SilvaT. BargerJ. PaquetteS. PatelH. PattersonS. AllenC.M. Protein farnesyltransferase and protein prenylation in Plasmodium falciparum.J. Biol. Chem.200227744420664207310.1074/jbc.M202860200 12194969
    [Google Scholar]
  127. NagarajV.A. SundaramB. VaradarajanN.M. SubramaniP.A. KalappaD.M. GhoshS.K. PadmanabanG. Malaria parasite-synthesized heme is essential in the mosquito and liver stages and complements host heme in the blood stages of infection.PLoS Pathog.201398e100352210.1371/journal.ppat.1003522 23935500
    [Google Scholar]
  128. van DoorenG.G. KennedyA.T. McFaddenG.I. The use and abuse of heme in apicomplexan parasites.Antioxid. Redox Signal.201217463465610.1089/ars.2012.4539 22320355
    [Google Scholar]
  129. JomaaH. WiesnerJ. SanderbrandS. AltincicekB. WeidemeyerC. HintzM. TürbachovaI. EberlM. ZeidlerJ. LichtenthalerH.K. SoldatiD. BeckE. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs.Science199928554331573157610.1126/science.285.5433.1573 10477522
    [Google Scholar]
  130. BorrmannS. IssifouS. EsserG. AdegnikaA.A. RamharterM. MatsieguiP.B. OyakhiromeS. Mawili-MboumbaD.P. MissinouM.A. KunJ.F.J. JomaaH. KremsnerP.G. Fosmidomycin-clindamycin for the treatment of Plasmodium falciparum malaria.J. Infect. Dis.200419091534154010.1086/424603 15478056
    [Google Scholar]
  131. HuyN.T. KameiK. KondoY. SeradaS. EanaoriK. TakanoR. TajimaK. HaraS. Effect of antifungal azoles on the heme detoxification system of malarial parasite.J. Biochem.2002131343744410.1093/oxfordjournals.jbchem.a003119 11872173
    [Google Scholar]
  132. Simão-GurgeR.M. WunderlichG. CriccoJ.A. CubillosE.F.G. Doménech-CarbóA. Cebrián-TorrejónG. AlmeidaF.G. CirulliB.A. KatzinA.M. Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway.Sci. Rep.2019911926110.1038/s41598‑019‑55506‑y 31848371
    [Google Scholar]
  133. ToyamaT. TaharaM. NagamuneK. ArimitsuK. HamashimaY. PalacpacN.M.Q. KawaideH. HoriiT. TanabeK. Gibberellin biosynthetic inhibitors make human malaria parasite Plasmodium falciparum cells swell and rupture to death.PLoS One201273e3224610.1371/journal.pone.0032246 22412858
    [Google Scholar]
  134. NagarajV.A. PadmanabanG. Insights on heme synthesis in the malaria parasite.Trends Parasitol.201733858358610.1016/j.pt.2017.04.005 28495484
    [Google Scholar]
  135. KeH. SigalaP.A. MiuraK. MorriseyJ.M. MatherM.W. CrowleyJ.R. HendersonJ.P. GoldbergD.E. LongC.A. VaidyaA.B. The heme biosynthesis pathway is essential for Plasmodium falciparum development in mosquito stage but not in blood stages.J. Biol. Chem.201428950348273483710.1074/jbc.M114.615831 25352601
    [Google Scholar]
  136. SatoS. CloughB. CoatesL. WilsonR.J. Enzymes for heme biosynthesis are found in both the mitochondrion and plastid of the malaria parasite Plasmodium falciparum.Protist2004155111712510.1078/1434461000169 15144063
    [Google Scholar]
  137. BondayZ.Q. TaketaniS. GuptaP.D. PadmanabanG. Heme biosynthesis by the malarial parasite. Import of delta-aminolevulinate dehydrase from the host red cell.J. Biol. Chem.199727235218392184610.1074/jbc.272.35.21839 9268315
    [Google Scholar]
  138. GoldbergD.E. SigalaP.A. Plasmodium heme biosynthesis: To be or not to be essential?PLoS Pathog.2017139e100651110.1371/journal.ppat.1006511 28957449
    [Google Scholar]
  139. SigalaP.A. CrowleyJ.R. HendersonJ.P. GoldbergD.E. Deconvoluting heme biosynthesis to target blood-stage malaria parasites.eLife20154e0914310.7554/eLife.09143 26173178
    [Google Scholar]
  140. VaidA. RanjanR. SmytheW.A. HoppeH.C. SharmaP. PfPI3K, a phosphatidylinositol-3 kinase from Plasmodium falciparum, is exported to the host erythrocyte and is involved in hemoglobin trafficking.Blood2010115122500250710.1182/blood‑2009‑08‑238972 20093402
    [Google Scholar]
  141. AdelusiT.I. BolajiO.Q. OjoT.O. AdegunI.P. AdebodunS. Molecular mechanics with generalized born surface area (MMGBSA) calculations and docking studies unravel some antimalarial compounds using heme o synthase as therapeutic target.ChemistrySelect2023848e20230368610.1002/slct.202303686
    [Google Scholar]
  142. van NiekerkD.D. PenklerG.P. du ToitF. SnoepJ.L. Targeting glycolysis in the malaria parasite Plasmodium falciparum.FEBS J.2016283463464610.1111/febs.13615 26648082
    [Google Scholar]
  143. FisherG.M. CobboldS.A. JezewskiA. CarpenterE.F. ArnoldM. CowellA.N. TjhinE.T. SalibaK.J. Skinner-AdamsT.S. LeeM.C.S. Odom JohnA. WinzelerE.A. McConvilleM.J. PoulsenS.A. AndrewsK.T. The key glycolytic enzyme phosphofructokinase is involved in resistance to antiplasmodial glycosides.MBio2020116e02842e2010.1128/mBio.02842‑20 33293381
    [Google Scholar]
  144. AlamA. NeyazM.K. Ikramul HasanS. Exploiting unique structural and functional properties of malarial glycolytic enzymes for antimalarial drug development.Malar. Res. Treat.2014201411310.1155/2014/451065 25580350
    [Google Scholar]
  145. LinY.H. SataniN. HammoudiN. YanV.C. BarekatainY. KhadkaS. AckroydJ.J. GeorgiouD.K. PhamC.D. ArthurK. MaxwellD. PengZ. LeonardP.G. CzakoB. PisaneschiF. MandalP. SunY. ZielinskiR. PandoS.C. WangX. TranT. XuQ. WuQ. JiangY. KangZ. AsaraJ.M. PriebeW. BornmannW. MarszalekJ.R. DePinhoR.A. MullerF.L. An enolase inhibitor for the targeted treatment of ENO1-deleted cancers.Nat. Metab.20202121413142610.1038/s42255‑020‑00313‑3 33230295
    [Google Scholar]
  146. ShivapurkarR. HingamireT. KulkarniA.S. RajamohananP.R. ReddyD.S. ShanmugamD. Evaluating antimalarial efficacy by tracking glycolysis in Plasmodium falciparum using NMR spectroscopy.Sci. Rep.2018811807610.1038/s41598‑018‑36197‑3 30584241
    [Google Scholar]
  147. ChanM. TanD.S.H. SimT.S. Plasmodium falciparum pyruvate kinase as a novel target for antimalarial drug-screening.Travel Med. Infect. Dis.20075212513110.1016/j.tmaid.2006.01.015 17298920
    [Google Scholar]
  148. AvereschN.J.H. KrömerJ.O. Metabolic engineering of the shikimate pathway for production of aromatics and derived compounds—present and future strain construction strategies.Front. Bioeng. Biotechnol.201863210.3389/fbioe.2018.00032 29632862
    [Google Scholar]
  149. McConkeyG.A. Targeting the shikimate pathway in the malaria parasite Plasmodium falciparum.Antimicrob. Agents Chemother.199943117517710.1128/AAC.43.1.175 9869588
    [Google Scholar]
  150. RobertsC.W. RobertsF. LyonsR.E. KirisitsM.J. MuiE.J. FinnertyJ. JohnsonJ.J. FergusonD.J.P. CogginsJ.R. KrellT. CoombsG.H. MilhousW.K. KyleD.E. TziporiS. BarnwellJ. DameJ.B. CarltonJ. McLeodR. The shikimate pathway and its branches in apicomplexan parasites.J. Infect. Dis.2002185s1Suppl. 1S25S3610.1086/338004 11865437
    [Google Scholar]
  151. ValencianoA.L. Fernández-MurgaM.L. MerinoE.F. HoldermanN.R. ButschekG.J. ShafferK.J. TylerP.C. CasseraM.B. Metabolic dependency of chorismate in Plasmodium falciparum suggests an alternative source for the ubiquinone biosynthesis precursor.Sci. Rep.2019911393610.1038/s41598‑019‑50319‑5 31558748
    [Google Scholar]
  152. ReichauS. JiaoW. WalkerS.R. HuttonR.D. BakerE.N. ParkerE.J. Potent inhibitors of a shikimate pathway enzyme from Mycobacterium tuberculosis: combining mechanism- and modeling-based design.J. Biol. Chem.201128618161971620710.1074/jbc.M110.211649 21454647
    [Google Scholar]
  153. Zulet-GonzálezA. Barco-AntoñanzasM. Gil-MonrealM. RoyuelaM. ZabalzaA. Increased glyphosate-induced gene expression in the shikimate pathway is abolished in the presence of aromatic amino acids and mimicked by shikimate.Front. Plant Sci.20201145910.3389/fpls.2020.00459 32411158
    [Google Scholar]
  154. MaedaH. DudarevaN. The shikimate pathway and aromatic amino Acid biosynthesis in plants.Annu. Rev. Plant Biol.20126317310510.1146/annurev‑arplant‑042811‑105439 22554242
    [Google Scholar]
  155. McRobertL. JiangS. SteadA. McConkeyG.A. Plasmodium falciparum: Interaction of shikimate analogues with antimalarial drugs.Exp. Parasitol.2005111317818110.1016/j.exppara.2005.07.002 16140296
    [Google Scholar]
  156. HydeJ.E. Exploring the folate pathway in Plasmodium falciparum.Acta Trop.200594319120610.1016/j.actatropica.2005.04.002 15845349
    [Google Scholar]
  157. MagnaniG. LomazziM. PeracchiA. Completing the folate biosynthesis pathway in Plasmodium falciparum: p -aminobenzoate is produced by a highly divergent promiscuous aminodeoxychorismate lyase.Biochem. J.2013455214915510.1042/BJ20130896 23957380
    [Google Scholar]
  158. NzilaA. WardS.A. MarshK. SimsP.F.G. HydeJ.E. Comparative folate metabolism in humans and malaria parasites (part I): Pinters for malaria treatment from cancer chemotherapy.Trends Parasitol.200521629229810.1016/j.pt.2005.04.002 15922251
    [Google Scholar]
  159. CowmanA.F. FooteS.J. Chemotherapy and drug resistance in malaria.Int. J. Parasitol.199020450351310.1016/0020‑7519(90)90198‑V 2210944
    [Google Scholar]
  160. KainK.C. Current status and replies to frequently posed questions on atovaquone plus proguanil (Malarone) for the prevention of malaria.BioDrugs200317Suppl. 1232810.2165/00063030‑200317001‑00006 12785875
    [Google Scholar]
  161. RiboldiG.P. ZigweidR. MylerP.J. MayclinS.J. CouñagoR.M. StakerB.L. Identification of P218 as a potent inhibitor of Mycobacterium ulcerans DHFR.RSC Med. Chem.202112110310910.1039/D0MD00303D 34046602
    [Google Scholar]
  162. YuthavongY. TarnchompooB. VilaivanT. ChitnumsubP. KamchonwongpaisanS. CharmanS.A. McLennanD.N. WhiteK.L. VivasL. BongardE. ThongphanchangC. TaweechaiS. VanichtanankulJ. RattanajakR. ArwonU. FantauzziP. YuvaniyamaJ. CharmanW.N. MatthewsD. Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target.Proc. Natl. Acad. Sci. USA201210942168231682810.1073/pnas.1204556109 23035243
    [Google Scholar]
  163. RathodP.K. Malaria chemotherapy: Paradigms from pyrimidine metabolism. Biol. Parasit. TschudiC. PearceE.J. Boston, MASpringer US2000739310.1007/978‑1‑4757‑4622‑8_4
    [Google Scholar]
  164. BeleteT.M. Recent progress in the development of new antimalarial drugs with novel targets.Drug Des. Devel. Ther.2020143875388910.2147/DDDT.S265602 33061294
    [Google Scholar]
  165. KamchonwongpaisanS. QuarrellR. CharoensetakulN. PonsinetR. VilaivanT. VanichtanankulJ. TarnchompooB. SirawarapornW. LoweG. YuthavongY. Inhibitors of multiple mutants of Plasmodium falciparum dihydrofolate reductase and their antimalarial activities.J. Med. Chem.200447367368010.1021/jm030165t 14736247
    [Google Scholar]
  166. CobboldS.A. MartinR.E. KirkK. Methionine transport in the malaria parasite Plasmodium falciparum.Int. J. Parasitol.201141112513510.1016/j.ijpara.2010.09.001 20851123
    [Google Scholar]
  167. AsawamahasakdaW. YuthavongY. The methionine synthesis cycle and salvage of methyltetrahydrofolate from host red cells in the malaria parasite (Plasmodium falciparum).Parasitology1993107111010.1017/S0031182000079348 8355992
    [Google Scholar]
  168. MarreirosI.M. MarquesS. ParreiraA. MastrodomenicoV. MounceB.C. HarrisC.T. KafsackB.F. BillkerO. Zuzarte-LuísV. MotaM.M. A non-canonical sensing pathway mediates Plasmodium adaptation to amino acid deficiency.Commun. Biol.20236120510.1038/s42003‑023‑04566‑y 36810637
    [Google Scholar]
  169. MusabyimanaJ.P. DistlerU. SassmannshausenJ. BerksC. MantiJ. BenninkS. BlaschkeL. BurdaP.C. FlammersfeldA. TenzerS. NgwaC.J. PradelG. Plasmodium falciparum S-adenosylmethionine synthetase is essential for parasite survival through a complex interaction network with cytoplasmic and nuclear proteins.Microorganisms2022107141910.3390/microorganisms10071419 35889137
    [Google Scholar]
  170. AnvariB. Leading causes of methotrexate and antimalarial drugs discontinuation in Iranian patients with rheumatoid arthritis.Egypt. Rheumatol.201638314715210.1016/j.ejr.2015.12.003
    [Google Scholar]
  171. ImwongM. RussellB. SuwanaruskR. NzilaA. LeimanisM.L. SriprawatK. KaewpongsriS. PhyoA.P. SnounouG. NostenF. ReniaL. Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax.J. Infect. Dis.2011203220721010.1093/infdis/jiq024 21288820
    [Google Scholar]
  172. TheraM.A. SehdevP.S. CoulibalyD. TraoreK. GarbaM.N. CissokoY. KoneA. GuindoA. DickoA. BeavoguiA.H. DjimdeA.A. LykeK.E. DialloD.A. DoumboO.K. PloweC.V. Impact of trimethoprim-sulfamethoxazole prophylaxis on falciparum malaria infection and disease.J. Infect. Dis.2005192101823182910.1086/498249 16235184
    [Google Scholar]
  173. ChemalyS.M. ChenC.T. van ZylR.L. Naturally occurring cobalamins have antimalarial activity.J. Inorg. Biochem.2007101576477310.1016/j.jinorgbio.2007.01.006 17343914
    [Google Scholar]
  174. DownieM.J. KirkK. MamounC.B. Purine salvage pathways in the intraerythrocytic malaria parasite Plasmodium falciparum.Eukaryot. Cell2008781231123710.1128/EC.00159‑08 18567789
    [Google Scholar]
  175. FrameI.J. DeniskinR. AroraA. AkabasM.H. Purine import into malaria parasites as a target for antimalarial drug development.Ann. N. Y. Acad. Sci.201513421192810.1111/nyas.12568 25424653
    [Google Scholar]
  176. MinnowY.V.T. SchrammV.L. Purine and pyrimidine pathways as antimalarial targets. Infect. Paolo PiccalugaP. Dis., IntechOpen202310.5772/intechopen.106468
    [Google Scholar]
  177. BabaiR. IzraelR. VértessyB.G. Characterization of the dynamics of Plasmodium falciparum deoxynucleotide-triphosphate pool in a stage-specific manner.Sci. Rep.20221211992610.1038/s41598‑022‑23807‑4 36402851
    [Google Scholar]
  178. RamanJ. AshokC.S. SubbayyaS.I.N. AnandR.P. SelviS.T. BalaramH. Plasmodium falciparum hypoxanthine guanine phosphoribosyltransferase. Stability studies on the product-activated enzyme.FEBS J.200527281900191110.1111/j.1742‑4658.2005.04620.x 15819884
    [Google Scholar]
  179. DonaldsonT. KimK. Targeting Plasmodium falciparum purine salvage enzymes: A look at structure-based drug development.Infect. Disord. Drug Targets201010319119910.2174/187152610791163408 20480551
    [Google Scholar]
  180. KeoughD.T. HockováD. JanebaZ. WangT.H. NaesensL. EdsteinM.D. ChavchichM. GuddatL.W. Aza-acyclic nucleoside phosphonates containing a second phosphonate group as inhibitors of the human, Plasmodium falciparum and vivax 6-oxopurine phosphoribosyltransferases and their prodrugs as antimalarial agents.J. Med. Chem.201558282784610.1021/jm501416t 25494538
    [Google Scholar]
  181. ShiW. TingL.M. KicskaG.A. LewandowiczA. TylerP.C. EvansG.B. FurneauxR.H. KimK. AlmoS.C. SchrammV.L. Plasmodium falciparum purine nucleoside phosphorylase: Crystal structures, immucillin inhibitors, and dual catalytic function.J. Biol. Chem.200427918181031810610.1074/jbc.C400068200 14982926
    [Google Scholar]
  182. HazletonK.Z. HoM.C. CasseraM.B. ClinchK. CrumpD.R. RosarioI.Jr MerinoE.F. AlmoS.C. TylerP.C. SchrammV.L. Acyclic immucillin phosphonates: second-generation inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase.Chem. Biol.201219672173010.1016/j.chembiol.2012.04.012 22726686
    [Google Scholar]
  183. ChevietT. Lefebvre-TournierI. WeinS. PeyrottesS. Plasmodium purine metabolism and its inhibition by nucleoside and nucleotide analogues.J. Med. Chem.201962188365839110.1021/acs.jmedchem.9b00182 30964283
    [Google Scholar]
  184. TingL.M. ShiW. LewandowiczA. SinghV. MwakingweA. BirckM.R. RingiaE.A.T. BenchG. MadridD.C. TylerP.C. EvansG.B. FurneauxR.H. SchrammV.L. KimK. Targeting a novel Plasmodium falciparum purine recycling pathway with specific immucillins.J. Biol. Chem.2005280109547955410.1074/jbc.M412693200 15576366
    [Google Scholar]
  185. BarrettM. The pentose phosphate pathway and parasitic protozoa.Parasitol. Today1997131111610.1016/S0169‑4758(96)10075‑2 15275160
    [Google Scholar]
  186. AllenS.M. LimE.E. JortzikE. PreussJ. ChuaH.H. MacRaeJ.I. RahlfsS. HaeusslerK. DowntonM.T. McConvilleM.J. BeckerK. RalphS.A. Plasmodium falciparum glucose‐6‐phosphate dehydrogenase 6‐phosphogluconolactonase is a potential drug target.FEBS J.2015282193808382310.1111/febs.13380 26198663
    [Google Scholar]
  187. ZuluagaL. ParraS. GarridoE. López-MuñozR. MayaJ.D. BlairS. Dehydroepiandrosterone effect on Plasmodium falciparum and its interaction with antimalarial drugs.Exp. Parasitol.2013133111412010.1016/j.exppara.2012.11.002 23178659
    [Google Scholar]
  188. HaeusslerK. Fritz-WolfK. ReichmannM. RahlfsS. BeckerK. Characterization of Plasmodium falciparum 6-Phosphogluconate Dehydrogenase as an Antimalarial Drug Target.J. Mol. Biol.2018430214049406710.1016/j.jmb.2018.07.030 30098336
    [Google Scholar]
  189. KarthikaA. HemavathyN. AmalaM. RajamanikandanS. VeerapandianM. PrabhuD. VetrivelU. Jung ChenC. Jeyaraj PandianC. JeyakanthanJ. Structural and functional characterization of 6-phosphogluconate dehydrogenase in Plasmodium falciparum (3D7) and identification of its potent inhibitors.J. Biomol. Struct. Dyn.20244242058207410.1080/07391102.2023.2248271 37599457
    [Google Scholar]
  190. KöhlerE. BarrachH.J. NeubertD. Inhibition of NADP dependent oxidoreductases by the 6‐aminonicotinamide analogue of NADP.FEBS Lett.19706322522810.1016/0014‑5793(70)80063‑1 11947380
    [Google Scholar]
  191. BoatengR.A. Tastan BishopÖ. MusyokaT.M. Characterisation of plasmodial transketolases and identification of potential inhibitors: An in silico study.Malar. J.202019144210.1186/s12936‑020‑03512‑1 33256744
    [Google Scholar]
  192. HikosakaK. KomatsuyaK. SuzukiS. KitaK. Mitochondria of malaria parasites as a drug target. Overv. SamieA. Trop. Dis., InTech201510.5772/61283
    [Google Scholar]
  193. PainterH.J. MorriseyJ.M. VaidyaA.B. Mitochondrial electron transport inhibition and viability of intraerythrocytic Plasmodium falciparum.Antimicrob. Agents Chemother.201054125281528710.1128/AAC.00937‑10 20855748
    [Google Scholar]
  194. FisherN. AntoineT. WardS.A. BiaginiG.A. Mitochondrial electron transport chain of Plasmodium falciparum. Encycl. Malar. HommelM. KremsnerP.G. New YorkSpringer201411410.1007/978‑1‑4614‑8757‑9_12‑1
    [Google Scholar]
  195. NixonG.L. PidathalaC. ShoneA.E. AntoineT. FisherN. O’NeillP.M. WardS.A. BiaginiG.A. Targeting the mitochondrial electron transport chain of Plasmodium falciparum: new strategies towards the development of improved antimalarials for the elimination era.Future Med. Chem.20135131573159110.4155/fmc.13.121 24024949
    [Google Scholar]
  196. BiaginiG.A. FisherN. ShoneA.E. MubarakiM.A. SrivastavaA. HillA. AntoineT. WarmanA.J. DaviesJ. PidathalaC. AmewuR.K. LeungS.C. SharmaR. GibbonsP. HongD.W. PacorelB. LawrensonA.S. CharoensutthivarakulS. TaylorL. BergerO. MbekeaniA. StocksP.A. NixonG.L. ChadwickJ. HemingwayJ. DelvesM.J. SindenR.E. ZeemanA.M. KockenC.H.M. BerryN.G. O’NeillP.M. WardS.A. Generation of quinolone antimalarials targeting the Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria.Proc. Natl. Acad. Sci. USA2012109218298830310.1073/pnas.1205651109 22566611
    [Google Scholar]
  197. KeH. GanesanS.M. DassS. MorriseyJ.M. PouS. NilsenA. RiscoeM.K. MatherM.W. VaidyaA.B. Mitochondrial type II NADH dehydrogenase of Plasmodium falciparum (PfNDH2) is dispensable in the asexual blood stages.PLoS One2019144e021402310.1371/journal.pone.0214023 30964863
    [Google Scholar]
  198. OrrA.L. AshokD. SarantosM.R. NgR. ShiT. GerencserA.A. HughesR.E. BrandM.D. Novel inhibitors of mitochondrial sn-glycerol 3-phosphate dehydrogenase.PLoS One201492e8993810.1371/journal.pone.0089938 24587137
    [Google Scholar]
  199. LunevS. BatistaF.A. BoschS.S. WrengerC. GrovesM.R. Identification and validation of novel drug targets for the treatment of Plasmodium falciparum malaria: New insights. Current Topics in Malaria. Rodriguez-MoralesA.J. InTech201610.5772/65659
    [Google Scholar]
  200. Mi-IchiF. MiyaderaH. KobayashiT. TakamiyaS. WakiS. IwataS. ShibataS. KitaK. Parasite mitochondria as a target of chemotherapy: inhibitory effect of licochalcone A on the Plasmodium falciparum respiratory chain.Ann. N. Y. Acad. Sci.200510561465410.1196/annals.1352.037 16387676
    [Google Scholar]
  201. ItoT. KajitaS. FujiiM. ShinoharaY. Plasmodium Parasite Malate-Quinone Oxidoreductase Functionally Complements a Yeast Deletion Mutant of Mitochondrial Malate Dehydrogenase.Microbiol. Spectr.2023113e00168e2310.1128/spectrum.00168‑23 37036365
    [Google Scholar]
  202. EsserL. XiaD. Mitochondrial cytochrome bc1 complex as validated drug target: A structural perspective.Trop. Med. Infect. Dis.2024923910.3390/tropicalmed9020039 38393128
    [Google Scholar]
  203. SheokandP.K. MühleipA. SheinerL. Plasmodium falciparum mitochondrial complex III, the target of atovaquone, is essential for progression to the transmissible sexual stages.Preprints2024
    [Google Scholar]
  204. AmporndanaiK. PinthongN. O’NeillP.M. HongW.D. AmewuR.K. PidathalaC. BerryN.G. LeungS.C. WardS.A. BiaginiG.A. HasnainS.S. AntonyukS.V. Targeting the Ubiquinol-Reduction (Qi) Site of the Mitochondrial Cytochrome bc1 Complex for the Development of Next Generation Quinolone Antimalarials.Biology2022118110910.3390/biology11081109 35892964
    [Google Scholar]
  205. BiaginiG.A. FisherN. BerryN. StocksP.A. MeunierB. WilliamsD.P. Bonar-LawR. BrayP.G. OwenA. O’NeillP.M. WardS.A. Acridinediones: selective and potent inhibitors of the malaria parasite mitochondrial bc1 complex.Mol. Pharmacol.20087351347135510.1124/mol.108.045120 18319379
    [Google Scholar]
  206. CapperM.J. O’NeillP.M. FisherN. StrangeR.W. MossD. WardS.A. BerryN.G. LawrensonA.S. HasnainS.S. BiaginiG.A. AntonyukS.V. Antimalarial 4(1H)-pyridones bind to the Q i site of cytochrome bc1.Proc. Natl. Acad. Sci. USA2015112375576010.1073/pnas.1416611112 25564664
    [Google Scholar]
  207. JenkinsB.J. DalyT.M. MorriseyJ.M. MatherM.W. VaidyaA.B. BergmanL.W. Characterization of a Plasmodium falciparum Orthologue of the Yeast Ubiquinone-Binding Protein, Coq10p.PLoS One2016113e015219710.1371/journal.pone.0152197 27015086
    [Google Scholar]
  208. KumarS. BhardwajT.R. PrasadD.N. SinghR.K. Drug targets for resistant malaria: Historic to future perspectives.Biomed. Pharmacother.201810482710.1016/j.biopha.2018.05.009 29758416
    [Google Scholar]
  209. NurkantoA. ImamuraR. RahmawatiY. PrabandariE.E. WaluyoD. AnnouraT. YamamotoK. SekijimaM. NishimuraY. OkabeT. ShibaT. ShibataN. KojimaH. DuffyJ. NozakiT. Dephospho-CoenzymeA. Dephospho-Coenzyme A Kinase Is an Exploitable Drug Target against Plasmodium falciparum: Identification of Selective Inhibitors by High-Throughput Screening of a Large Chemical Compound Library.Antimicrob. Agents Chemother.20226611e00420e0042210.1128/aac.00420‑22 36314787
    [Google Scholar]
  210. AgrawalP. KumariS. MohmmedA. MalhotraP. SharmaU. SahalD. Identification of novel, potent, and selective compounds against malaria using glideosomal-associated protein 50 as a drug target.ACS Omega2023841385063852310.1021/acsomega.3c05323 37867646
    [Google Scholar]
  211. FieldS.K. Bedaquiline for the treatment of multidrug-resistant tuberculosis: Great promise or disappointment?Ther. Adv. Chronic Dis.20156417018410.1177/2040622315582325 26137207
    [Google Scholar]
  212. NinaP.B. MorriseyJ.M. GanesanS.M. KeH. PershingA.M. MatherM.W. VaidyaA.B. ATP synthase complex of Plasmodium falciparum: Dimeric assembly in mitochondrial membranes and resistance to genetic disruption.J. Biol. Chem.201128648413124132210.1074/jbc.M111.290973 21984828
    [Google Scholar]
  213. KrungkraiS.R. KrungkraiJ. Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target.Asian Pac. J. Trop. Med.20169652553410.1016/j.apjtm.2016.04.012 27262062
    [Google Scholar]
  214. CasseraM.B. ZhangY. HazletonK.Z. SchrammV.L. Purine and pyrimidine pathways as targets in Plasmodium falciparum.Curr. Top. Med. Chem.201111162103211510.2174/156802611796575948 21619511
    [Google Scholar]
  215. HartutiE.D. SakuraT. TagodM.S.O. YoshidaE. WangX. MochizukiK. AcharjeeR. MatsuoY. TokumasuF. MoriM. WaluyoD. ShiomiK. NozakiT. HamanoS. ShibaT. KitaK. InaokaD.K. Identification of 3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine Derivatives as Novel Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase.Int. J. Mol. Sci.20212213723610.3390/ijms22137236 34281290
    [Google Scholar]
  216. KokkondaS. El MazouniF. WhiteK.L. WhiteJ. ShacklefordD.M. Lafuente-MonasterioM.J. RowlandP. ManjalanagaraK. JosephJ.T. Garcia-PérezA. FernandezJ. GamoF.J. WatersonD. BurrowsJ.N. PalmerM.J. CharmanS.A. RathodP.K. PhillipsM.A. Isoxazolopyrimidine-based inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase with antimalarial activity.ACS Omega2018389227924010.1021/acsomega.8b01573 30197997
    [Google Scholar]
  217. PhillipsM.A. WhiteK.L. KokkondaS. DengX. WhiteJ. El MazouniF. MarshK. TomchickD.R. ManjalanagaraK. RudraK.R. WirjanataG. NoviyantiR. PriceR.N. MarfurtJ. ShacklefordD.M. ChiuF.C.K. CampbellM. Jimenez-DiazM.B. BazagaS.F. Angulo-BarturenI. MartinezM.S. Lafuente-MonasterioM. KaminskyW. SilueK. ZeemanA.M. KockenC. LeroyD. BlascoB. RossignolE. RueckleT. MatthewsD. BurrowsJ.N. WatersonD. PalmerM.J. RathodP.K. CharmanS.A. A triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with improved drug-like properties for treatment and prevention of malaria.ACS Infect. Dis.201621294595710.1021/acsinfecdis.6b00144 27641613
    [Google Scholar]
  218. LebanJ. KralikM. MiesJ. BaumgartnerR. GassenM. TaslerS. Biphenyl-4-ylcarbamoyl thiophene carboxylic acids as potent DHODH inhibitors.Bioorg. Med. Chem. Lett.200616226727010.1016/j.bmcl.2005.10.011 16246558
    [Google Scholar]
  219. DickermanB.K. ElsworthB. CobboldS.A. NieC.Q. McConvilleM.J. CrabbB.S. GilsonP.R. Identification of inhibitors that dually target the new permeability pathway and dihydroorotate dehydrogenase in the blood stage of Plasmodium falciparum.Sci. Rep.2016613750210.1038/srep37502 27874068
    [Google Scholar]
  220. OlszewskiK.L. MatherM.W. MorriseyJ.M. GarciaB.A. VaidyaA.B. RabinowitzJ.D. LlinásM. Branched tricarboxylic acid metabolism in Plasmodium falciparum.Nature2010466730777477810.1038/nature09301 20686576
    [Google Scholar]
  221. MacRaeJ.I. DixonM.W.A. DearnleyM.K. ChuaH.H. ChambersJ.M. KennyS. BottovaI. TilleyL. McConvilleM.J. Mitochondrial metabolism of sexual and asexual blood stages of the malaria parasite Plasmodium falciparum.BMC Biol.20131116710.1186/1741‑7007‑11‑67 23763941
    [Google Scholar]
  222. OlszewskiK.L. LlinásM. Central carbon metabolism of Plasmodium parasites.Mol. Biochem. Parasitol.201117529510310.1016/j.molbiopara.2010.09.001 20849882
    [Google Scholar]
  223. EbstieY.A. AbayS.M. TadesseW.T. EjiguD.A. Tafenoquine and its potential in the treatment and relapse prevention of Plasmodium vivax malaria: The evidence to date.Drug Des. Devel. Ther.2016102387239910.2147/DDDT.S61443 27528800
    [Google Scholar]
  224. LuK.Y. DerbyshireE.R. Tafenoquine: A step toward malaria elimination.Biochemistry202059891192010.1021/acs.biochem.9b01105 32073254
    [Google Scholar]
  225. LindblomJ.C.R. ZhangX. LehaneA.M. A pH fingerprint assay to identify inhibitors of multiple validated and potential antimalarial drug targets.ACS Infect. Dis.20241041185120010.1021/acsinfecdis.3c00588 38499199
    [Google Scholar]
  226. HuangJ. YuanY. ZhaoN. PuD. TangQ. ZhangS. LuoS. YangX. WangN. XiaoY. ZhangT. LiuZ. Sakata-KatoT. JiangX. KatoN. YanN. YinH. Orthosteric-allosteric dual inhibitors of PfHT1 as selective antimalarial agents.Proc. Natl. Acad. Sci. USA20211183e201774911810.1073/pnas.2017749118 33402433
    [Google Scholar]
  227. KraftT.E. ArmstrongC. HeitmeierM.R. OdomA.R. HruzP.W. The glucose transporter PfHT1 is an antimalarial target of the HIV protease inhibitor lopinavir.Antimicrob. Agents Chemother.201559106203620910.1128/AAC.00899‑15 26248369
    [Google Scholar]
  228. WichersJ.S. van GelderC. FuchsG. RugeJ.M. PietschE. FerreiraJ.L. SafaviS. von ThienH. BurdaP.C. Mesén-RamirezP. SpielmannT. StraussJ. GilbergerT.W. BachmannA. Characterization of apicomplexan amino acid transporters (ApiATs) in the malaria parasite Plasmodium falciparum.MSphere202166e00743e2110.1128/mSphere.00743‑21 34756057
    [Google Scholar]
  229. HeitmeierM.R. HreskoR.C. EdwardsR.L. PrinsenM.J. IlaganM.X.G. Odom JohnA.R. HruzP.W. Identification of druggable small molecule antagonists of the Plasmodium falciparum hexose transporter PfHT and assessment of ligand access to the glucose permeation pathway via FLAG-mediated protein engineering.PLoS One2019145e021645710.1371/journal.pone.0216457 31071153
    [Google Scholar]
  230. EndoT. TakemaeH. SharmaI. FuruyaT. Multipurpose drugs active against both Plasmodium spp. and Microorganisms: Potential application for new drug development.Front. Cell. Infect. Microbiol.20211179750910.3389/fcimb.2021.797509 35004357
    [Google Scholar]
  231. FedeleA.O. ProudC.G. Chloroquine and bafilomycin A mimic lysosomal storage disorders and impair mTORC1 signalling.Biosci. Rep.2020404BSR2020090510.1042/BSR20200905 32285908
    [Google Scholar]
  232. MurithiJ.M. PascalC. BathJ. BoulencX. GnädigN.F. PasajeC.F.A. RubianoK. YeoT. MokS. KlieberS. DesertP. Jiménez-DíazM.B. MarfurtJ. RouillierM. Cherkaoui-RbatiM.H. GobeauN. WittlinS. UhlemannA.C. PriceR.N. WirjanataG. NoviyantiR. TumwebazeP. CooperR.A. RosenthalP.J. SanzL.M. GamoF.J. JosephJ. SinghS. BashyamS. AugereauJ.M. GiraudE. BozecT. VermatT. TuffalG. GuillonJ.M. MenegottoJ. SalléL. LouitG. CabanisM.J. NicolasM.F. DoubovetzkyM. MerinoR. BessilaN. Angulo-BarturenI. BaudD. BebrevskaL. EscudiéF. NilesJ.C. BlascoB. CampbellS. CourtemancheG. FraisseL. PelletA. FidockD.A. LeroyD. The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to Plasmodium falciparum parasite resistance.Sci. Transl. Med.202113603eabg601310.1126/scitranslmed.abg6013 34290058
    [Google Scholar]
  233. SanchezC. The malaria food channel.Nat. Rev. Microbiol.20119748410.1038/nrmicro2606 21677682
    [Google Scholar]
  234. GaurA.H. PanettaJ.C. SmithA.M. DallasR.H. FreemanB.B.III StewartT.B. TangL. JohnE. BranumK.C. PatelN.D. OstS. HeineR.N. RichardsonJ.L. HammillJ.T. BebrevskaL. GusovskyF. MakiN. YanagiT. FlynnP.M. McCarthyJ.S. ChalonS. GuyR.K. Combining SJ733, an oral ATP4 inhibitor of Plasmodium falciparum, with the pharmacokinetic enhancer cobicistat: An innovative approach in antimalarial drug development.EBioMedicine20228010406510.1016/j.ebiom.2022.104065 35598441
    [Google Scholar]
  235. HoC.M. BeckJ.R. LaiM. CuiY. GoldbergD.E. EgeaP.F. ZhouZ.H. Malaria parasite translocon structure and mechanism of effector export.Nature20185617721707510.1038/s41586‑018‑0469‑4 30150771
    [Google Scholar]
  236. MatthewsK. KalanonM. ChisholmS.A. SturmA. GoodmanC.D. DixonM.W.A. SandersP.R. NeblT. FraserF. HaaseS. McFaddenG.I. GilsonP.R. CrabbB.S. de Koning-WardT.F. TheP lasmodium translocon of exported proteins (PTEX) component thioredoxin‐2 is important for maintaining normal blood‐stage growth.Mol. Microbiol.20138961167118610.1111/mmi.12334 23869529
    [Google Scholar]
  237. AhiyaA.I. BhatnagarS. MorriseyJ.M. BeckJ.R. VaidyaA.B. Dramatic consequences of reducing erythrocyte membrane cholesterol on Plasmodium falciparum.Microbiol. Spectr.2022101e00158e2210.1128/spectrum.00158‑22 35196803
    [Google Scholar]
  238. IstvanE.S. DasS. BhatnagarS. BeckJ.R. OwenE. LlinasM. GanesanS.M. NilesJ.C. WinzelerE. VaidyaA.B. GoldbergD.E. Plasmodium Niemann-Pick type C1-related protein is a druggable target required for parasite membrane homeostasis.eLife20198e4052910.7554/eLife.40529 30888318
    [Google Scholar]
  239. LyuM. SuC.C. KazuraJ.W. YuE.W. Structural basis of transport and inhibition of the Plasmodium falciparum transporter PfFNT.EMBO Rep.2021223e5162810.15252/embr.202051628 33471955
    [Google Scholar]
  240. PengX. WangN. ZhuA. XuH. LiJ. ZhouY. WangC. XiaoQ. GuoL. LiuF. JiaZ. DuanH. HuJ. YuanW. GengJ. YanC. JiangX. DengD. Structural characterization of the Plasmodium falciparum lactate transporter PfFNT alone and in complex with antimalarial compound MMV007839 reveals its inhibition mechanism.PLoS Biol.2021199e300138610.1371/journal.pbio.3001386 34499638
    [Google Scholar]
  241. KandepeduN. Gonzàlez CabreraD. EedubilliS. TaylorD. BrunschwigC. GibhardL. NjorogeM. LawrenceN. PaquetT. EyermannC.J. SpangenbergT. BasarabG.S. StreetL.J. ChibaleK. Identification, characterization, and optimization of 2,8-Disubstituted-1,5-naphthyridines as Novel Plasmodium falciparum phosphatidylinositol-4-kinase inhibitors with in vivo efficacy in a humanized mouse model of malaria.J. Med. Chem.201861135692570310.1021/acs.jmedchem.8b00648 29889526
    [Google Scholar]
  242. BrunschwigC. LawrenceN. TaylorD. AbayE. NjorogeM. BasarabG.S. Le ManachC. PaquetT. CabreraD.G. NchindaA.T. de KockC. WiesnerL. DentiP. WatersonD. BlascoB. LeroyD. WittyM.J. DoniniC. DuffyJ. WittlinS. WhiteK.L. CharmanS.A. Jiménez-DíazM.B. Angulo-BarturenI. HerrerosE. GamoF.J. RochfordR. MancamaD. CoetzerT.L. van der WattM.E. ReaderJ. BirkholtzL.M. MarshK.C. SolapureS.M. BurkeJ.E. McPhailJ.A. VanaerschotM. FidockD.A. FishP.V. SieglP. SmithD.A. WirjanataG. NoviyantiR. PriceR.N. MarfurtJ. SilueK.D. StreetL.J. ChibaleK. UCT943, a next-generation Plasmodium falciparum PI4K inhibitor preclinical candidate for the treatment of malaria.Antimicrob. Agents Chemother.2018629e00012e0001810.1128/AAC.00012‑18 29941635
    [Google Scholar]
  243. ChakrabartiM. JoshiN. KumariG. SinghP. ShoaibR. MunjalA. KumarV. BehlA. AbidM. GargS. GuptaS. SinghS. Interaction of Plasmodium falciparum apicortin with α- and β-tubulin is critical for parasite growth and survival.Sci. Rep.2021111468810.1038/s41598‑021‑83513‑5 33633135
    [Google Scholar]
  244. KumariG. JainR. Kumar SahR. KaliaI. VashisthaM. SinghP. Prasad SinghA. SambyK. BurrowsJ. SinghS. Multistage and transmission-blocking tubulin targeting potent antimalarial discovered from the open access MMV pathogen box.Biochem. Pharmacol.202220311515410.1016/j.bcp.2022.115154 35798201
    [Google Scholar]
  245. MorrissetteN. AbbaaliI. RamakrishnanC. HehlA.B. The tubulin superfamily in apicomplexan parasites.Microorganisms20231170610.3390/microorganisms11030706
    [Google Scholar]
  246. ZhangG. NiuG. Hooker-RomeraD. ShabaniS. RamelowJ. WangX. ButlerN.S. JamesA.A. LiJ. Targeting plasmodium α-tubulin-1 to block malaria transmission to mosquitoes.Front. Cell. Infect. Microbiol.202313113264710.3389/fcimb.2023.1132647 37009496
    [Google Scholar]
  247. FennellB.J. NaughtonJ.A. DempseyE. BellA. Cellular and molecular actions of dinitroaniline and phosphorothioamidate herbicides on Plasmodium falciparum: Tubulin as a specific antimalarial target.Mol. Biochem. Parasitol.2006145222623810.1016/j.molbiopara.2005.08.020 16406111
    [Google Scholar]
  248. HirstW.G. FachetD. KuropkaB. WeiseC. SalibaK.J. ReberS. Purification of functional Plasmodium falciparum tubulin allows for the identification of parasite-specific microtubule inhibitors.Curr. Biol.2022324919926.e610.1016/j.cub.2021.12.049 35051355
    [Google Scholar]
  249. MauerS. CamargoN. AbatiyowB.A. GargaroO.R. KappeS.H.I. KumarS. Plasmodium microtubule-binding protein EB1 is critical for partitioning of nuclei in male gametogenesis.MBio2023144e00822e0082310.1128/mbio.00822‑23 37535401
    [Google Scholar]
  250. TalmanA.M. DomarleO. McKenzieF. ArieyF. RobertV. Gametocytogenesis: The puberty of Plasmodium falciparum.Malar. J.2004312410.1186/1475‑2875‑3‑24 15253774
    [Google Scholar]
  251. KiszewskiA.E. Blocking Plasmodium falciparum malaria transmission with drugs: The gametocytocidal and sporontocidal properties of current and prospective antimalarials.Pharmaceuticals201041446810.3390/ph4010044
    [Google Scholar]
  252. ChawlaJ. OberstallerJ. AdamsJ.H. Targeting gametocytes of the malaria parasite Plasmodium falciparum in a functional genomics era: Next steps.Pathogens202110334610.3390/pathogens10030346 33809464
    [Google Scholar]
  253. DashM. SachdevaS. BansalA. SinhaA. Gametogenesis in Plasmodium: Delving deeper to connect the dots.Front. Cell. Infect. Microbiol.20221287790710.3389/fcimb.2022.877907 35782151
    [Google Scholar]
  254. LaurensM.B. RTS,S/AS01 vaccine (Mosquirix™): An overview.Hum. Vaccin. Immunother.202016348048910.1080/21645515.2019.1669415 31545128
    [Google Scholar]
  255. MacraildC.A. AndersR.F. FoleyM. NortonR.S. Apical membrane antigen 1 as an anti-malarial drug target.Curr. Top. Med. Chem.201111162039204710.2174/156802611796575885 21619512
    [Google Scholar]
  256. FernandesP. LoubensM. Le BorgneR. MarinachC. ArdinB. BriquetS. VincensiniL. HamadaS. Hoareau-CoudertB. VerbavatzJ.M. WeinerA. SilvieO. The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts.PLoS Pathog.2022186e101064310.1371/journal.ppat.1010643 35731833
    [Google Scholar]
  257. DluzewskiA.R. LingI.T. HopkinsJ.M. GraingerM. MargosG. MitchellG.H. HolderA.A. BannisterL.H. Formation of the food vacuole in Plasmodium falciparum: A potential role for the 19 kDa fragment of merozoite surface protein 1 (MSP1(19)).PLoS One200838e308510.1371/journal.pone.0003085 18769730
    [Google Scholar]
  258. JäschkeA. CoulibalyB. RemarqueE.J. BujardH. EppC. Merozoite Surface protein 1 from Plasmodium falciparum is a major target of opsonizing antibodies in individuals with acquired immunity against Malaria.Clin. Vaccine Immunol.20172411e00155e1710.1128/CVI.00155‑17 28877929
    [Google Scholar]
  259. CollinsC.R. HackettF. HowellS.A. SnijdersA.P. RussellM.R.G. CollinsonL.M. BlackmanM.J. The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion.eLife20209e6112110.7554/eLife.61121 33287958
    [Google Scholar]
  260. NavaS. WhiteA.C.Jr Castellanos-GonzálezA. Cryptosporidium parvum subtilisin-like serine protease (SUB1) is crucial for parasite egress from host cells.Infect. Immun.2019875e00784e1810.1128/IAI.00784‑18 30782859
    [Google Scholar]
  261. GallentiR. PoklepovichT. Florin-ChristensenM. SchnittgerL. The repertoire of serine rhomboid proteases of piroplasmids of importance to animal and human health.Int. J. Parasitol.202151645546210.1016/j.ijpara.2020.10.010 33610524
    [Google Scholar]
  262. TaylorH.M. McRobertL. GraingerM. SicardA. DluzewskiA.R. HoppC.S. HolderA.A. BakerD.A. The malaria parasite cyclic GMP-dependent protein kinase plays a central role in blood-stage schizogony.Eukaryot. Cell201091374510.1128/EC.00186‑09 19915077
    [Google Scholar]
  263. VanaerschotM. MurithiJ.M. PasajeC.F.A. Ghidelli-DisseS. DwomohL. BirdM. SpottiswoodeN. MittalN. ArendseL.B. OwenE.S. WichtK.J. SicilianoG. BöscheM. YeoT. KumarT.R.S. MokS. CarpenterE.F. GiddinsM.J. SanzO. OttilieS. AlanoP. ChibaleK. LlinásM. UhlemannA.C. DelvesM. TobinA.B. DoerigC. WinzelerE.A. LeeM.C.S. NilesJ.C. FidockD.A. Inhibition of resistance-refractory P. falciparum Kinase PKG delivers prophylactic, blood stage, and transmission-blocking antiplasmodial activity.Cell Chem. Biol.2020277806816.e810.1016/j.chembiol.2020.04.001 32359426
    [Google Scholar]
  264. KimC. SharmaR. Cyclic nucleotide selectivity of protein kinase G isozymes.Protein Sci.202130231632710.1002/pro.4008 33271627
    [Google Scholar]
  265. CheukaP.M. CentaniL. ArendseL.B. FienbergS. WambuaL. RengaS.S. DziwornuG.A. KumarM. LawrenceN. TaylorD. WittlinS. CoertzenD. ReaderJ. van der WattM. BirkholtzL.M. ChibaleK. New Amidated 3,6-Diphenylated Imidazopyridazines with Potent Antiplasmodium Activity Are Dual Inhibitors of Plasmodium Phosphatidylinositol-4-kinase and cGMP-Dependent Protein Kinase.ACS Infect. Dis.202171344610.1021/acsinfecdis.0c00481 33319990
    [Google Scholar]
  266. BakerD.A. StewartL.B. LargeJ.M. BowyerP.W. AnsellK.H. Jiménez-DíazM.B. El BakkouriM. BirchallK. DecheringK.J. BoulocN.S. CoombsP.J. WhalleyD. HardingD.J. Smiljanic-HurleyE. WheldonM.C. WalkerE.M. DessensJ.T. LafuenteM.J. SanzL.M. GamoF.J. FerrerS.B. HuiR. BousemaT. Angulo-BarturénI. MerrittA.T. CroftS.L. GutteridgeW.E. KettleboroughC.A. OsborneS.A. A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission.Nat. Commun.20178143010.1038/s41467‑017‑00572‑x 28874661
    [Google Scholar]
  267. Le BihanA. de KanterR. Angulo-BarturenI. BinkertC. BossC. BrunR. BrunnerR. BuchmannS. BurrowsJ. DecheringK.J. DelvesM. EwerlingS. FerrerS. FischliC. Gamo-BenitoF.J. GnädigN.F. HeidmannB. Jiménez-DíazM.B. LeroyD. MartínezM.S. MeyerS. MoehrleJ.J. NgC.L. NoviyantiR. RueckerA. SanzL.M. SauerweinR.W. ScheurerC. SchleiferboeckS. SindenR. SnyderC. StraimerJ. WirjanataG. MarfurtJ. PriceR.N. WellerT. FischliW. FidockD.A. ClozelM. WittlinS. Characterization of novel antimalarial compound ACT-451840: Preclinical assessment of activity and dose-efficacy modeling.PLoS Med.20161310e100213810.1371/journal.pmed.1002138 27701420
    [Google Scholar]
  268. JohnG.K. DouglasN.M. von SeidleinL. NostenF. BairdJ.K. WhiteN.J. PriceR.N. Primaquine radical cure of Plasmodium vivax: A critical review of the literature.Malar. J.201211128010.1186/1475‑2875‑11‑280 22900786
    [Google Scholar]
  269. NeblT. De VeerM.J. SchofieldL. Stimulation of innate immune responses by malarial glycosylphosphatidylinositol via pattern recognition receptors.Parasitology2005130S1Suppl.S45S6210.1017/S0031182005008152 16281992
    [Google Scholar]
  270. JonsdottirT.K. ElsworthB. CobboldS. GabrielaM. PloegerE. Parkyn SchneiderM. CharnaudS.C. DansM.G. McConvilleM. BullenH.E. CrabbB.S. GilsonP.R. PTEX helps efficiently traffic haemoglobinases to the food vacuole in Plasmodium falciparum.PLoS Pathog.2023197e101100610.1371/journal.ppat.1011006 37523385
    [Google Scholar]
  271. AdovelandeJ. DelèzeJ. SchrévelJ. Synergy between two calcium channel blockers, verapamil and fantofarone (SR33557), in reversing chloroquine resistance in Plasmodium falciparum.Biochem. Pharmacol.199855443344010.1016/S0006‑2952(97)00482‑6 9514077
    [Google Scholar]
  272. JoyS. ThirunavukkarasuL. AgrawalP. SinghA. SagarB.K.C. ManjithayaR. SuroliaN. Basal and starvation-induced autophagy mediates parasite survival during intraerythrocytic stages of Plasmodium falciparum.Cell Death Discov.2018414310.1038/s41420‑018‑0107‑9 30302277
    [Google Scholar]
  273. HainA.U.P. BoschJ. Autophagy in Plasmodium, a multifunctional pathway?Comput. Struct. Biotechnol. J.2013811e20130800210.5936/csbj.201308002 24688742
    [Google Scholar]
  274. LeleuI. AllooJ. CazenaveP.A. RolandJ. PiedS. Autophagy pathways in the genesis of plasmodium-derived microvesicles: A double-edged sword?Life202212341510.3390/life12030415 35330166
    [Google Scholar]
  275. IqbalM.S. SiddiquiA.A. AlamA. GoyalM. BanerjeeC. SarkarS. MazumderS. DeR. NagS. SahaS.J. BandyopadhyayU. Expression, purification and characterization of Plasmodium falciparum vacuolar protein sorting 29.Protein Expr. Purif.201612071510.1016/j.pep.2015.12.004
    [Google Scholar]
  276. AgrawalP. ManjithayaR. SuroliaN. Autophagy‐related protein Pf ATG18 participates in food vacuole dynamics and autophagy‐like pathway in Plasmodium falciparum.Mol. Microbiol.2020113476678210.1111/mmi.14441 31863491
    [Google Scholar]
  277. WiserM.F. The digestive vacuole of the malaria parasite: A specialized lysosome.Pathogens202413318210.3390/pathogens13030182 38535526
    [Google Scholar]
  278. Al-BariM.A.A. Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases.Pharmacol. Res. Perspect.201751e0029310.1002/prp2.293 28596841
    [Google Scholar]
  279. AlderA. SanchezC.P. RussellM.R.G. CollinsonL.M. LanzerM. BlackmanM.J. GilbergerT.W. MatzJ.M. The role of Plasmodium V-ATPase in vacuolar physiology and antimalarial drug uptake.Proc. Natl. Acad. Sci. USA202312030e230642012010.1073/pnas.2306420120 37463201
    [Google Scholar]
  280. YangY. HuL. ZhengH. MaoC. HuW. XiongK. WangF. LiuC. Application and interpretation of current autophagy inhibitors and activators.Acta Pharmacol. Sin.201334562563510.1038/aps.2013.5 23524572
    [Google Scholar]
  281. ChaudhariR. SharmaS. PatankarS. Glutathione and thioredoxin systems of the malaria parasite Plasmodium falciparum: Partners in crime?Biochem. Biophys. Res. Commun.201748819510010.1016/j.bbrc.2017.05.015 28479253
    [Google Scholar]
  282. LushchakV.I. Glutathione homeostasis and functions: Potential targets for medical interventions.J. Amino Acids2012201273683710.1155/2012/736837
    [Google Scholar]
  283. KanzokS.M. SchirmerR.H. TürbachovaI. IozefR. BeckerK. The thioredoxin system of the malaria parasite Plasmodium falciparum. Glutathione reduction revisited.J. Biol. Chem.200027551401804018610.1074/jbc.M007633200 11013257
    [Google Scholar]
  284. McCartyS. SchellenbergerA. GoodwinD. FuantaN. TekwaniB. CalderónA. Plasmodium falciparum Thioredoxin reductase (PfTrxR) and its role as a target for new antimalarial discovery.Molecules2015206114591147310.3390/molecules200611459 26111176
    [Google Scholar]
  285. SinghD.V. MisraK. Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site.Bioinformation20094518719210.6026/97320630004187 20461157
    [Google Scholar]
  286. SannellaA.R. CasiniA. GabbianiC. MessoriL. BiliaA.R. VincieriF.F. MajoriG. SeveriniC. New uses for old drugs. Auranofin, a clinically established antiarthritic metallodrug, exhibits potent antimalarial effects in vitro: Mechanistic and pharmacological implications.FEBS Lett.2008582684484710.1016/j.febslet.2008.02.028 18294965
    [Google Scholar]
  287. FärberP.M. ArscottL.D. WilliamsC.H.Jr BeckerK. SchirmerR.H. Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue.FEBS Lett.1998422331131410.1016/S0014‑5793(98)00031‑3 9498806
    [Google Scholar]
  288. LuG. NagbanshiM. GoldauN. Mendes JorgeM. MeissnerP. JahnA. MockenhauptF.P. MüllerO. Efficacy and safety of methylene blue in the treatment of malaria: A systematic review.BMC Med.20181615910.1186/s12916‑018‑1045‑3 29690878
    [Google Scholar]
  289. SchirmerR.H. CoulibalyB. StichA. ScheiweinM. MerkleH. EubelJ. BeckerK. BecherH. MüllerO. ZichT. SchiekW. KouyatéB. Methylene blue as an antimalarial agent.Redox Rep.20038527227510.1179/135100003225002899 14962363
    [Google Scholar]
  290. CampbellT.L. De SilvaE.K. OlszewskiK.L. ElementoO. LlinásM. Identification and genome-wide prediction of DNA binding specificities for the ApiAP2 family of regulators from the malaria parasite.PLoS Pathog.2010610e100116510.1371/journal.ppat.1001165 21060817
    [Google Scholar]
  291. WangM. TangT. LiR. HuangZ. LingD. ZhengL. DingY. LiuT. XuW. ZhuF. MinH. BoonhokR. MaoF. ZhuJ. LiX. JiangL. LiJ. Drug repurposing of quisinostat to discover novel Plasmodium falciparum HDAC1 inhibitors with enhanced triple-stage antimalarial activity and improved safety.J. Med. Chem.20226554156418110.1021/acs.jmedchem.1c01993 35175762
    [Google Scholar]
  292. AndrewsK.T. TranT.N. LuckeA.J. KahnbergP. LeG.T. BoyleG.M. GardinerD.L. Skinner-AdamsT.S. FairlieD.P. K. P, L. Gt, B. Gm, G. Dl, S.-A. Ts, F. Dp, Potent antimalarial activity of histone deacetylase inhibitor analogues.Antimicrob. Agents Chemother.20085241454146110.1128/AAC.00757‑07
    [Google Scholar]
  293. ThompsonT.A. ChahineZ. Le RochK.G. The role of long noncoding RNAs in malaria parasites.Trends Parasitol.202339751753110.1016/j.pt.2023.03.016 37121862
    [Google Scholar]
  294. DoolanD.L. DobañoC. BairdJ.K. Acquired immunity to malaria.Clin. Microbiol. Rev.2009221133610.1128/CMR.00025‑08 19136431
    [Google Scholar]
  295. LongC.A. ZavalaF. Immune responses in Malaria.Cold Spring Harb. Perspect. Med.201778a02557710.1101/cshperspect.a025577 28389518
    [Google Scholar]
  296. RobsonK.J. FrevertU. ReckmannI. CowanG. BeierJ. ScraggI.G. TakeharaK. BishopD.H. PradelG. SindenR. Thrombospondin-related adhesive protein (TRAP) of Plasmodium falciparum: expression during sporozoite ontogeny and binding to human hepatocytes.EMBO J.199514163883389410.1002/j.1460‑2075.1995.tb00060.x 7664729
    [Google Scholar]
  297. NolandG.S. JansenP. VululeJ.M. ParkG.S. OndigoB.N. KazuraJ.W. MoormannA.M. JohnC.C. Effect of transmission intensity and age on subclass antibody responses to Plasmodium falciparum pre-erythrocytic and blood-stage antigens.Acta Trop.2015142475610.1016/j.actatropica.2014.10.011 25446174
    [Google Scholar]
  298. ShuklaS. ManiA. Immunoinformatics and vaccine development. Unraveling New Front. ChaudharyA. SethiS.K. VermaA. SingaporeSpringer Nature202411513110.1007/978‑981‑97‑7123‑3_6
    [Google Scholar]
  299. BonamS.R. RéniaL. TadepalliG. BayryJ. KumarH.M.S. Plasmodium falciparum Malaria vaccines and vaccine adjuvants.Vaccines2021910107210.3390/vaccines9101072 34696180
    [Google Scholar]
  300. SunC. ZhouB. The molecular and cellular action properties of artemisinins: What has yeast told us?Microb. Cell20163519620510.15698/mic2016.05.498 28357355
    [Google Scholar]
  301. AngK.K.H. HolmesM.J. HigaT. HamannM.T. KaraU.A.K. In vivo antimalarial activity of the beta-carboline alkaloid manzamine A.Antimicrob. Agents Chemother.20004461645164910.1128/AAC.44.6.1645‑1649.2000 10817722
    [Google Scholar]
  302. MiyaokaH. ShimomuraM. KimuraH. YamadaY. KimH.S. YusukeW. Antimalarial activity of kalihinol A and new relative diterpenoids from the Okinawan sponge, Acanthella sp.Tetrahedron19985444134671347410.1016/S0040‑4020(98)00818‑7
    [Google Scholar]
  303. LuZ. DingY. LiX.C. DjigbenouD.R. GrimbergB.T. FerreiraD. IrelandC.M. Van WagonerR.M. 3-Bromohomofascaplysin A, a fascaplysin analogue from a Fijian Didemnum sp. ascidian.Bioorg. Med. Chem.201119226604660710.1016/j.bmc.2011.05.046 21696970
    [Google Scholar]
  304. UadiaP.O. EzeamuzieI.C. LadanM.J. GerretsR. Antimalarial activity of cyclosporins A, C and D.Afr. J. Med. Med. Sci.19942314751 7839946
    [Google Scholar]
  305. KeitaA. FranetichJ.F. CarrazM. ValentinL. BordessoulesM. BaronL. BigeardP. DupuyF. GeayV. TefitM. SarrasinV. MichelS. LavazecC. HouzéS. MazierD. SoulardV. PoréeF.H. DuvalR. Potent antiplasmodial derivatives of dextromethorphan reveal the Ent-morphinan pharmacophore of tazopsine-type alkaloids.Pharmaceutics202214237210.3390/pharmaceutics14020372 35214104
    [Google Scholar]
  306. HouëlE. StienD. BourdyG. DeharoE. Quassinoids: Anticancer and antimalarial activities. Nat. Prod., Springer Berlin Heidelberg, Berlin. RamawatK.G. MérillonJ-M. Heidelberg20133775380210.1007/978‑3‑642‑22144‑6_161
    [Google Scholar]
  307. ForkuoA.D. AnsahC. MensahK.B. AnnanK. GyanB. TheronA. MancamaD. WrightC.W. In vitro anti-malarial interaction and gametocytocidal activity of cryptolepine.Malar. J.201716149610.1186/s12936‑017‑2142‑z 29282057
    [Google Scholar]
  308. MensahK.B. BennehC. ForkuoA.D. AnsahC. Cryptolepine, the main alkaloid of the antimalarial Cryptolepis sanguinolenta (Lindl.) schlechter, induces malformations in zebrafish embryos.Biochem. Res. Int.20192019707698610.1155/2019/7076986
    [Google Scholar]
  309. RajuR. KhalilZ.G. PiggottA.M. BlumenthalA. GardinerD.L. Skinner-AdamsT.S. CaponR.J. MollemycinA. Mollemycin A: An antimalarial and antibacterial glyco-hexadepsipeptide-polyketide from an Australian marine-derived Streptomyces sp. (CMB-M0244).Org. Lett.20141661716171910.1021/ol5003913 24611932
    [Google Scholar]
  310. BürstnerN. RoggoS. OstermannN. BlankJ. DelmasC. FreulerF. GerhartzB. HinnigerA. HoepfnerD. LiechtyB. MihalicM. MurphyJ. PistoriusD. RottmannM. ThomasJ.R. SchirleM. SchmittE.K. Gift from nature: Cyclomarin A kills mycobacteria and malaria parasites by distinct modes of action.ChemBioChem201516172433243610.1002/cbic.201500472 26472355
    [Google Scholar]
  311. PrasharC. ThakurN. ChakrabortiS. Areeb HussainS.S. VashishtK. PandeyK.C. The landscape of nature-derived antimalarials-potential of marine natural products in countering the evolving Plasmodium.Front. Drug Discov.20222106523110.3389/fddsv.2022.1065231
    [Google Scholar]
  312. KishoreV. YarlaN. BishayeeA. PuttaS. MallaR. NeelapuN. ChallaS. DasS. ShiralgiY. HegdeG. DhananjayaB. Multi-targeting andrographolide and its natural analogs as potential therapeutic agents.Curr. Top. Med. Chem.201717884585710.2174/1568026616666160927150452 27697058
    [Google Scholar]
  313. IndradiR.B. MuhaiminM. BarlianaM.I. KhatibA. Potential plant-based new antiplasmodial agent used in Papua Island, Indonesia.Plants2023129181310.3390/plants12091813 37176870
    [Google Scholar]
  314. MishraK. DashA.P. DeyN. Andrographolide: A novel antimalarial diterpene lactone compound from Andrographis paniculata and its interaction with curcumin and artesunate.J. Trop. Med.201120111610.1155/2011/579518 21760808
    [Google Scholar]
  315. AchanJ. TalisunaA.O. ErhartA. YekaA. TibenderanaJ.K. BaliraineF.N. RosenthalP.J. D’AlessandroU. Quinine, an old anti-malarial drug in a modern world: Role in the treatment of malaria.Malar. J.201110114410.1186/1475‑2875‑10‑144 21609473
    [Google Scholar]
  316. LuzziG.A. PetoT.E.A. Adverse effects of antimalarials. An update.Drug Saf.19938429531110.2165/00002018‑199308040‑00004 8481216
    [Google Scholar]
  317. SilvaP.U.J. OliveiraM.B. VieiraW. CardosoS.V. BlumenbergC. FrancoA. SiqueiraW.L. ParanhosL.R. Oral pigmentation as an adverse effect of chloroquine and hydroxychloroquine use.Medicine202210111e2904410.1097/MD.0000000000029044 35356915
    [Google Scholar]
  318. ChatioS. AborigoR. AdongoP.B. AnyorigiyaT. DalinjongP.A. AkweongoP. OduroA. Factors influencing adverse events reporting within the health care system: The case of artemisinin-based combination treatments in northern Ghana.Malar. J.201615112510.1186/s12936‑016‑1172‑2 26921239
    [Google Scholar]
  319. IssaM.S. WarsameM. MahamatM.H.T. SalehI.D.M. BoulotigamK. DjimrassengarH. IssaA.H. AbdelkaderO. HassoumiM. DjimadoumM. Doderer-LangC. NdihiokubwayoJ.B. RasmussenC. MenardD. Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Chad: Clinical and genetic surveillance.Malar. J.202322124010.1186/s12936‑023‑04644‑w 37612601
    [Google Scholar]
  320. FlorimondC. de LavalF. EarlyA.M. SauthierS. LazrekY. PelleauS. MonteiroW.M. AgranierM. TaudonN. MorinF. MagrisM. LacerdaM.V.G. VianaG.M.R. HerreraS. AdhinM.R. FerreiraM.U. WoodrowC.J. AwabG.R. CoxH. AdeM.P. MosnierE. DjossouF. NeafseyD.E. RingwaldP. MussetL. Impact of piperaquine resistance in Plasmodium falciparum on malaria treatment effectiveness in The Guianas: A descriptive epidemiological study.Lancet Infect. Dis.202424216117110.1016/S1473‑3099(23)00502‑9 37858325
    [Google Scholar]
  321. PasayC.J. RockettR. SekuloskiS. GriffinP. MarquartL. PeateyC. WangC.Y.T. O’RourkeP. ElliottS. BakerM. MöhrleJ.J. McCarthyJ.S. Piperaquine monotherapy of drug-susceptible Plasmodium falciparum infection results in rapid clearance of parasitemia but is followed by the appearance of gametocytemia.J. Infect. Dis.2016214110511310.1093/infdis/jiw128 27056954
    [Google Scholar]
  322. AshleyE.A. RechtJ. WhiteN.J. Primaquine: the risks and the benefits.Malar. J.201413141810.1186/1475‑2875‑13‑418 25363455
    [Google Scholar]
  323. BragaC.B.E. MartinsA.C. CayotopaA.D.E. KleinW.W. SchlosserA.R. da SilvaA.F. de SouzaM.N. AndradeB.W.B. Filgueira-JúniorJ.A. Side effects of chloroquine and primaquine and symptom reduction in malaria endemic area (Mâncio Lima, Acre, Brazil).Interdiscip. Perspect. Infect. Dis.2015201534685310.1155/2015/346853
    [Google Scholar]
  324. TaylorW.R.J. ThriemerK. von SeidleinL. YuentrakulP. AssawariyathipatT. AssefaA. AuburnS. ChandK. ChauN.H. CheahP.Y. DongL.T. DhordaM. DegagaT.S. DevineA. EkawatiL.L. FahmiF. HailuA. HasanzaiM.A. HienT.T. KhuH. LeyB. LubellY. MarfurtJ. MohammadH. MooreK.A. NaddimM.N. PasaribuA.P. PasaribuS. PromnarateC. RahimA.G. SirithiranontP. SolomonH. SudoyoH. SutantoI. ThanhN.V. Tuyet-TrinhN.T. WaithiraN. WoyessaA. YaminF.Y. DondorpA. SimpsonJ.A. BairdJ.K. WhiteN.J. DayN.P. PriceR.N. Short-course primaquine for the radical cure of Plasmodium vivax malaria: A multicentre, randomised, placebo-controlled non-inferiority trial.Lancet20193941020292993810.1016/S0140‑6736(19)31285‑1 31327563
    [Google Scholar]
  325. BairdJ.K. Tafenoquine for travelers’ malaria: evidence, rationale and recommendations.J. Travel Med.2018251tay11010.1093/jtm/tay110 30380095
    [Google Scholar]
  326. AhmadS.S. RahiM. RanjanV. SharmaA. Mefloquine as a prophylaxis for malaria needs to be revisited.Int. J. Parasitol. Drugs Drug Resist.202117232610.1016/j.ijpddr.2021.06.003 34339933
    [Google Scholar]
  327. KokoV.S. WarsameM. VonhmB. JeuronlonM.K. MenardD. MaL. TawehF. TehmehL. NyansaiyeP. PrattO.J. ParwonS. KamaraP. AsinyaM. KollieA. RingwaldP. Artesunate-amodiaquine and artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Liberia: in vivo efficacy and frequency of molecular markers.Malar. J.202221113410.1186/s12936‑022‑04140‑7 35477399
    [Google Scholar]
  328. BouchaudO. ImbertP. TouzeJ.E. DodooA.N.O. DanisM. LegrosF. Fatal cardiotoxicity related to halofantrine: A review based on a worldwide safety data base.Malar. J.20098128910.1186/1475‑2875‑8‑289 20003315
    [Google Scholar]
  329. MonlunE. Le MetayerP. SzwandtS. NeauD. Longy-BoursierM. HortonJ. Le BrasM. Cardiac complications of halofantrine: A prospective study of 20 patients.Trans. R. Soc. Trop. Med. Hyg.199589443043310.1016/0035‑9203(95)90041‑1 7570888
    [Google Scholar]
  330. ChuW.Y. DorloT.P.C. Pyronaridine: A review of its clinical pharmacology in the treatment of malaria.J. Antimicrob. Chemother.202378102406241810.1093/jac/dkad260 37638690
    [Google Scholar]
  331. CroftS.L. DuparcS. Arbe-BarnesS.J. CraftJ.C. ShinC.S. FleckensteinL. Borghini-FuhrerI. RimH.J. Review of pyronaridine anti-malarial properties and product characteristics.Malar. J.201211127010.1186/1475‑2875‑11‑270 22877082
    [Google Scholar]
  332. NordmannT. BorrmannS. RamharterM. Drug-induced hypersensitivity to artemisinin-based therapies for malaria.Trends Parasitol.202238213614610.1016/j.pt.2021.08.011 34561157
    [Google Scholar]
  333. NostenF. WhiteN.J. Artemisinin-based combination treatment of falciparum malaria.Am. J. Trop. Med. Hyg.2007776_Suppl)(Suppl.18119210.4269/ajtmh.2007.77.18118165491
    [Google Scholar]
  334. AshtonT.M. FokasE. Kunz-SchughartL.A. FolkesL.K. AnbalaganS. HuetherM. KellyC.J. PirovanoG. BuffaF.M. HammondE.M. StratfordM. MuschelR.J. HigginsG.S. McKennaW.G. The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia.Nat. Commun.2016711230810.1038/ncomms12308 27453292
    [Google Scholar]
  335. BjörkmanA. Phillips-HowardP.A. Adverse reactions to sulfa drugs: implications for malaria chemotherapy.Bull. World Health Organ.1991693297304 1893504
    [Google Scholar]
  336. MarealleA.I. MbwamboD.P. MikomangwaW.P. KilonziM. MlyukaH.J. MutagondaR.F. A decade since sulfonamide-based anti-malarial medicines were limited for intermittent preventive treatment of malaria among pregnant women in Tanzania.Malar. J.201817140910.1186/s12936‑018‑2565‑1 30400908
    [Google Scholar]
  337. NjauJ.D. KabanywanyiA.M. GoodmanC.A. MacArthurJ.R. KapellaB.K. GimnigJ.E. KahigwaE. BlolandP.B. AbdullaS.M. KachurS.P. Adverse drug events resulting from use of drugs with sulphonamide-containing anti-malarials and artemisinin-based ingredients: findings on incidence and household costs from three districts with routine demographic surveillance systems in rural Tanzania.Malar. J.201312123610.1186/1475‑2875‑12‑236 23844934
    [Google Scholar]
  338. Health and Medicine Division, National Academies of Sciences, Engineering, and Medicine, Assessment of Long-Term Health Effects of Antimalarial Drugs When Used for Prophylaxis.Washington, D.C.National Academies Press202010.17226/25688
    [Google Scholar]
  339. GaillardT. MadametM. PradinesB. Tetracyclines in malaria.Malar. J.201514144510.1186/s12936‑015‑0980‑0 26555664
    [Google Scholar]
  340. BaumgärtnerF. JourdanJ. ScheurerC. BlascoB. CampoB. MäserP. WittlinS. In vitro activity of anti-malarial ozonides against an artemisinin-resistant isolate.Malar. J.20171614510.1186/s12936‑017‑1696‑0 28122617
    [Google Scholar]
  341. GunjanS. SharmaT. YadavK. ChauhanB.S. SinghS.K. SiddiqiM.I. TripathiR. Artemisinin derivatives and synthetic trioxane trigger apoptotic cell death in asexual stages of Plasmodium.Front. Cell. Infect. Microbiol.2018825610.3389/fcimb.2018.00256 30094226
    [Google Scholar]
  342. ShafiqN. RajagopalanS. KushwahaH.N. MittalN. ChandurkarN. BhallaA. KaurS. PandhiP. PuriG.D. AchuthanS. PareekA. SinghS.K. SrivastavaJ.S. GaurS.P.S. MalhotraS. Single ascending dose safety and pharmacokinetics of CDRI-97/78: First-in-human study of a novel antimalarial drug.Malar. Res. Treat.2014201437252110.1155/2014/372521
    [Google Scholar]
  343. NagelschmitzJ. VoithB. WensingG. RoemerA. FugmannB. HaynesR.K. KoteckaB.M. RieckmannK.H. EdsteinM.D. First assessment in humans of the safety, tolerability, pharmacokinetics, and ex vivo pharmacodynamic antimalarial activity of the new artemisinin derivative artemisone.Antimicrob. Agents Chemother.20085293085309110.1128/AAC.01585‑07 18559649
    [Google Scholar]
  344. ObaldiaN.III KoteckaB.M. EdsteinM.D. HaynesR.K. FugmannB. KyleD.E. RieckmannK.H. Evaluation of artemisone combinations in Aotus monkeys infected with Plasmodium falciparum.Antimicrob. Agents Chemother.20095383592359410.1128/AAC.00471‑09 19506062
    [Google Scholar]
  345. ChienH.D. PantaleoA. KeselyK.R. NoomunaP. PuttK.S. TuanT.A. LowP.S. TurriniF.M. Imatinib augments standard malaria combination therapy without added toxicity.J. Exp. Med.202121810e2021072410.1084/jem.20210724 34436509
    [Google Scholar]
  346. IqbalA. ChakrabortyJ. ChoudhuriS. NaikA. BhattacharyyaM. CML-004: Imatinib is protective against falciparum malaria: A case control study from a tertiary care centre in west bengal.Clin. Lymphoma Myeloma Leuk.202020S22910.1016/S2152‑2650(20)30485‑7
    [Google Scholar]
  347. KollerR. Mombo-NgomaG. GrobuschM.P. The early preclinical and clinical development of ganaplacide (KAF156), a novel antimalarial compound.Expert Opin. Investig. Drugs2018271080381010.1080/13543784.2018.1524871 30223692
    [Google Scholar]
  348. OgutuB. YekaA. KusemererwaS. ThompsonR. TintoH. ToureA.O. UthaisinC. VermaA. KibuukaA. LinganiM. LourençoC. Mombo-NgomaG. NdubaV. N’GuessanT.L. NassaG.J.W. NyantaroM. TinaL.O. SinghP.K. El GaaloulM. MarrastA.C. ChikotoH. CsermakK. DeminI. MehtaD. PathanR. RisterucciC. SuG. WinnipsC. KaguthiG. FofanaB. GrobuschM.P. Ganaplacide (KAF156) plus lumefantrine solid dispersion formulation combination for uncomplicated Plasmodium falciparum malaria: An open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial.Lancet Infect. Dis.20232391051106110.1016/S1473‑3099(23)00209‑8 37327809
    [Google Scholar]
  349. BouwmanS.A.M. Zoleko-ManegoR. RennerK.C. SchmittE.K. Mombo-NgomaG. GrobuschM.P. The early preclinical and clinical development of cipargamin (KAE609), a novel antimalarial compound.Travel Med. Infect. Dis.20203610176510.1016/j.tmaid.2020.101765
    [Google Scholar]
  350. NdayisabaG. YekaA. AsanteK.P. GrobuschM.P. KaritaE. MugerwaH. AsiimweS. OduroA. FofanaB. DoumbiaS. JainJ.P. BarsainyaS. Kullak-UblickG.A. SuG. SchmittE.K. CsermakK. GandhiP. HughesD. Hepatic safety and tolerability of cipargamin (KAE609), in adult patients with Plasmodium falciparum malaria: A randomized, phase II, controlled, dose-escalation trial in sub-Saharan Africa.Malar. J.202120147810.1186/s12936‑021‑04009‑1 34930267
    [Google Scholar]
  351. SchmittE.K. NdayisabaG. YekaA. AsanteK.P. GrobuschM.P. KaritaE. MugerwaH. AsiimweS. OduroA. FofanaB. DoumbiaS. SuG. Csermak RennerK. VenishettyV.K. SayyedS. StraimerJ. DeminI. BarsainyaS. BoultonC. GandhiP. Efficacy of cipargamin (KAE609) in a randomized, phase II dose-escalation study in adults in sub-saharan africa with uncomplicated Plasmodium falciparum malaria.Clin. Infect. Dis.202274101831183910.1093/cid/ciab716 34410358
    [Google Scholar]
  352. McCarthyJ.S. YalkinogluÖ. OdedraA. WebsterR. OeuvrayC. TappertA. BezuidenhoutD. GiddinsM.J. DhingraS.K. FidockD.A. MarquartL. WebbL. YinX. KhandelwalA. BagchusW.M. Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: A first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection study.Lancet Infect. Dis.202121121713172410.1016/S1473‑3099(21)00252‑8 34715032
    [Google Scholar]
  353. RottmannM. JonatB. GumppC. DhingraS.K. GiddinsM.J. YinX. BadoloL. GrecoB. FidockD.A. OeuvrayC. SpangenbergT. Preclinical antimalarial combination study of M5717, a Plasmodium falciparum elongation factor 2 inhibitor, and pyronaridine, a hemozoin formation inhibitor.Antimicrob. Agents Chemother.2020644e02181e1910.1128/AAC.02181‑19 32041711
    [Google Scholar]
  354. PaquetT. Le ManachC. CabreraD.G. YounisY. HenrichP.P. AbrahamT.S. LeeM.C.S. BasakR. Ghidelli-DisseS. Lafuente-MonasterioM.J. BantscheffM. RueckerA. BlagboroughA.M. ZakutanskyS.E. ZeemanA.M. WhiteK.L. ShacklefordD.M. MannilaJ. MorizziJ. ScheurerC. Angulo-BarturenI. MartínezM.S. FerrerS. SanzL.M. GamoF.J. ReaderJ. BothaM. DecheringK.J. SauerweinR.W. TungtaengA. VanachayangkulP. LimC.S. BurrowsJ. WittyM.J. MarshK.C. BodenreiderC. RochfordR. SolapureS.M. Jiménez-DíazM.B. WittlinS. CharmanS.A. DoniniC. CampoB. BirkholtzL.M. HansonK.K. DrewesG. KockenC.H.M. DelvesM.J. LeroyD. FidockD.A. WatersonD. StreetL.J. ChibaleK. Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase.Sci. Transl. Med.20179387eaad973510.1126/scitranslmed.aad9735 28446690
    [Google Scholar]
  355. SinxadiP. DoniniC. JohnstoneH. LangdonG. WiesnerL. AllenE. DuparcS. ChalonS. McCarthyJ.S. LorchU. ChibaleK. MöhrleJ. BarnesK.I. Safety, tolerability, pharmacokinetics, and antimalarial activity of the novel Plasmodium phosphatidylinositol 4-kinase inhibitor mmv390048 in healthy volunteers.Antimicrob. Agents Chemother.2020644e01896e1910.1128/AAC.01896‑19 31932368
    [Google Scholar]
  356. ChughlayM.F. El GaaloulM. DoniniC. CampoB. BerghmansP.J. LucardieA. MarxM.W. Cherkaoui-RbatiM.H. LangdonG. Angulo-BarturenI. VieraS. Rosanas-UrgellA. Van GeertruydenJ.P. ChalonS. Chemoprotective antimalarial activity of P218 against Plasmodium falciparum: A randomized, placebo-controlled volunteer infection study.Am. J. Trop. Med. Hyg.202110441348135810.4269/ajtmh.20‑1165 33556040
    [Google Scholar]
  357. PosayapisitN. PengonJ. PrommanaP. ShoramM. YuthavongY. UthaipibullC. KamchonwongpaisanS. JupatanakulN. Transgenic pyrimethamine-resistant plasmodium falciparum reveals transmission-blocking potency of P218, a novel antifolate candidate drug.Int. J. Parasitol.202151863564210.1016/j.ijpara.2020.12.002 33713651
    [Google Scholar]
  358. AlaithanH. KumarN. IslamM.Z. LiappisA.P. NavaV.E. Novel therapeutics for malaria.Pharmaceutics2023157180010.3390/pharmaceutics15071800 37513987
    [Google Scholar]
  359. LeitgebA.M. CharunwatthanaP. RueangveerayutR. UthaisinC. SilamutK. ChotivanichK. SilaP. MollK. LeeS.J. LindgrenM. HolmerE. FärnertA. KiwuwaM.S. KristensenJ. HerderC. TarningJ. WahlgrenM. DondorpA.M. Inhibition of merozoite invasion and transient de-sequestration by sevuparin in humans with Plasmodium falciparum malaria.PLoS One20171212e018875410.1371/journal.pone.0188754 29244851
    [Google Scholar]
  360. VaroR. CrowleyV.M. MucasseH. SitoeA. BramugyJ. SerghidesL. WeckmanA.M. EriceC. BilaR. VitorinoP. MucasseC. ValenteM. AjanovicS. BalanzaN. ZhongK. DerpschY. GladstoneM. MayorA. BassatQ. KainK.C. Adjunctive rosiglitazone treatment for severe pediatric malaria: A randomized placebo-controlled trial in Mozambican children.Int. J. Infect. Dis.2024139344010.1016/j.ijid.2023.11.031 38013152
    [Google Scholar]
  361. LacerdaM.V.G. Llanos-CuentasA. KrudsoodS. LonC. SaundersD.L. MohammedR. YilmaD. Batista PereiraD. EspinoF.E.J. MiaR.Z. ChuquiyauriR. ValF. CasapíaM. MonteiroW.M. BritoM.A.M. CostaM.R.F. BuathongN. NoedlH. DiroE. GetieS. WubieK.M. AbdissaA. ZeynudinA. AbebeC. TadaM.S. BrandF. BeckH.P. AngusB. DuparcS. KleimJ.P. KellamL.M. RousellV.M. JonesS.W. HardakerE. MohamedK. CloverD.D. FletcherK. BretonJ.J. UgwuegbulamC.O. GreenJ.A. KohG.C.K.W. Single-dose tafenoquine to prevent relapse of Plasmodium vivax malaria.N. Engl. J. Med.2019380321522810.1056/NEJMoa1710775 30650322
    [Google Scholar]
  362. MaierJ.D. SiegfriedS. GültekinN. StangaZ. BairdJ.K. GrobuschM.P. SchlagenhaufP. Efficacy and safety of tafenoquine for malaria chemoprophylaxis (1998-2020): A systematic review and meta-analysis.Travel Med. Infect. Dis.20213910190810.1016/j.tmaid.2020.101908 33227500
    [Google Scholar]
  363. Llanos-CuentasA. CasapiaM. ChuquiyauriR. HinojosaJ.C. KerrN. RosarioM. TooveyS. ArchR.H. PhillipsM.A. RozenbergF.D. BathJ. NgC.L. CowellA.N. WinzelerE.A. FidockD.A. BakerM. MöhrleJ.J. Hooft van HuijsduijnenR. GobeauN. AraeipourN. AndenmattenN. RückleT. DuparcS. Antimalarial activity of single-dose DSM265, a novel plasmodium dihydroorotate dehydrogenase inhibitor, in patients with uncomplicated Plasmodium falciparum or Plasmodium vivax malaria infection: A proof-of-concept, open-label, phase 2a study.Lancet Infect. Dis.201818887488310.1016/S1473‑3099(18)30309‑8 29909069
    [Google Scholar]
  364. SulyokM. RückleT. RothA. MürbethR.E. ChalonS. KerrN. SamecS.S. GobeauN. CalleC.L. IbáñezJ. SulyokZ. HeldJ. GebruT. GranadosP. BrücknerS. NguetseC. MengueJ. LalremruataA. SimB.K.L. HoffmanS.L. MöhrleJ.J. KremsnerP.G. MordmüllerB. DSM265 for Plasmodium falciparum chemoprophylaxis: A randomised, double blinded, phase 1 trial with controlled human malaria infection.Lancet Infect. Dis.201717663664410.1016/S1473‑3099(17)30139‑1 28363637
    [Google Scholar]
  365. DomesR. FroschT. Investigations on the novel antimalarial ferroquine in biomimetic solutions using deep uv resonance raman spectroscopy and density functional theory.Anal. Chem.202395197630763910.1021/acs.analchem.3c00539 37141178
    [Google Scholar]
  366. TseE.G. KorsikM. ToddM.H. The past, present and future of anti-malarial medicines.Malar. J.20191819310.1186/s12936‑019‑2724‑z 30902052
    [Google Scholar]
  367. TaftB.R. YokokawaF. KirraneT. MataA.C. HuangR. BlaquiereN. WaldronG. ZouB. SimonO. VankadaraS. ChanW.L. DingM. SimS. StraimerJ. GuiguemdeA. LakshminarayanaS.B. JainJ.P. BodenreiderC. ThompsonC. LanshoeftC. ShuW. FangE. QumberJ. ChanK. PeiL. ChenY.L. SchulzH. LimJ. AbasS.N. AngX. LiuY. Angulo-BarturenI. Jiménez-DíazM.B. GamoF.J. Crespo-FernandezB. RosenthalP.J. CooperR.A. TumwebazeP. AguiarA.C.C. CampoB. CampbellS. WagnerJ. DiaganaT.T. SarkoC. Discovery and preclinical pharmacology of ine963, a potent and fast-acting blood-stage antimalarial with a high barrier to resistance and potential for single-dose cures in uncomplicated malaria.J. Med. Chem.20226553798381310.1021/acs.jmedchem.1c01995 35229610
    [Google Scholar]
  368. BoppS. PasajeC.F.A. SummersR.L. Magistrado-CoxenP. SchindlerK.A. Corpas-LopezV. YeoT. MokS. DeyS. SmickS. NasamuA.S. DemasA.R. MilneR. WiedemarN. CoreyV. Gomez-LorenzoM.D.G. FrancoV. EarlyA.M. LukensA.K. MilnerD. FurtadoJ. GamoF.J. WinzelerE.A. VolkmanS.K. DuffeyM. LaleuB. FidockD.A. WyllieS. NilesJ.C. WirthD.F. Potent acyl-CoA synthetase 10 inhibitors kill Plasmodium falciparum by disrupting triglyceride formation.Nat. Commun.2023141145510.1038/s41467‑023‑36921‑2 36927839
    [Google Scholar]
  369. GhoghariA.M. PatelH.V. NayakN.N. MansuriT.H. PillaiS.M. JainM.R. PatelH.B. KansagraK. RestaI.D. MöhrleJ. ParmarD.V. Simultaneous estimation of ZY-19489 and its active metabolite ZY-20486 in human plasma using LC-MS/MS, a novel antimalarial compound.Bioanalysis202113231761177710.4155/bio‑2021‑0194 34779650
    [Google Scholar]
  370. GaillardT. DormoiJ. MadametM. PradinesB. Macrolides and associated antibiotics based on similar mechanism of action like lincosamides in malaria.Malar. J.20161518510.1186/s12936‑016‑1114‑z 26873741
    [Google Scholar]
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